CN117025366A

CN117025366A - Biological filtration system

Info

Publication number: CN117025366A
Application number: CN202311006381.XA
Authority: CN
Inventors: 刘禹; 陈睿; 孙志远
Original assignee: Alite Biotechnology Shanghai Co ltd
Current assignee: Alite Biotechnology Shanghai Co ltd
Priority date: 2023-08-10
Filing date: 2023-08-10
Publication date: 2023-11-10

Abstract

The embodiment of the specification provides a biological filtration system, which comprises a biological reactor, a filtration device, a liquid chamber, a driving device and an integrated valve, wherein the driving device is connected with the liquid chamber and is used for providing power for filtering liquid in the biological reactor; the integrated valve is communicated with the bioreactor, the filtering device and the liquid chamber and is used for controlling the liquid to circulate at least two ways among the bioreactor, the filtering device and the liquid chamber so as to filter the liquid in the bioreactor.

Description

Biological filtration system

Technical Field

The present disclosure relates to the field of biological filtration, and more particularly to a biological filtration system.

Background

The biological filtration system refers to a system for treating or filtering a biological solution, which is used for a filtration process such as replacement of fresh culture solution, separation of cell metabolites, separation of cells from the culture solution, and the like. The traditional biological filtration system has a complex structure and a single filtration mode. For example, a biological filtration system can only achieve one fluid circulation pattern when alternating positive and negative pressures are applied. In order to realize multiple liquid circulation modes, multiple biological filtration systems with different pipeline connection modes are required. Therefore, it is necessary to provide a biological filtration system having a simple structure and various filtration modes.

Disclosure of Invention

One of the embodiments of the present disclosure provides a biological filtration system. The system comprises: the device comprises a bioreactor, a filtering device, a liquid chamber, a driving device and an integrated valve, wherein the driving device is connected with the liquid chamber and is used for providing power for filtering liquid in the bioreactor; the integrated valve is communicated with the bioreactor, the filtering device and the liquid chamber and is used for controlling the liquid to circulate at least two ways among the bioreactor, the filtering device and the liquid chamber so as to filter the liquid in the bioreactor.

In some embodiments, the biological filtration system further comprises a processor for controlling the integrated valve and the drive means to effect at least two circulating flows of liquid between the bioreactor, the filtration means and the liquid chamber based on the acquired information; and/or the liquid chamber comprises a first liquid chamber and a second liquid chamber, and/or the integrated valve comprises six branches, and the bioreactor, the filtering device and the liquid chamber are communicated through the six branches so as to realize circulation and circulation of liquid among the bioreactor, the filtering device and the liquid chamber; and/or the integrated valve comprises six branches, and each branch of the six branches comprises a switch for opening and closing the liquid circulation on the branch.

In some embodiments, the liquid chamber comprises a first liquid chamber and a second liquid chamber, the bioreactor comprising a first access port and a second access port; the filtering device comprises a first access port and a second access port; the first liquid chamber and the second liquid chamber each include a first end; the integrated valve comprises a first branch, a second branch, a third branch, a fourth branch, a fifth branch and a sixth branch, wherein the first end of the first liquid chamber is connected with the first inlet and outlet port through the first branch; the second access port is connected with the first access port through the second branch; the second inlet and outlet is connected with the first end of the second liquid chamber through the third branch; the first end of the first liquid chamber is connected with the second inlet and outlet through the fourth branch; the first access port is connected with the first inlet and outlet through the fifth branch; and the first end of the second liquid chamber is connected with the second access port through the sixth branch.

In some embodiments, the liquid chamber comprises a first liquid chamber and a second liquid chamber, the driving means comprises a positive pressure pump and a negative pressure pump, wherein the positive pressure pump is in communication with both the first liquid chamber and the second liquid chamber for driving liquid to flow from the first liquid chamber and/or the second liquid chamber to the bioreactor or the filtration means; the negative pressure pump is communicated with the first liquid chamber and the second liquid chamber and is used for driving liquid to flow from the bioreactor or the filtering device to the first liquid chamber and/or the second liquid chamber.

In some embodiments, the biological filtration system further comprises a processor for: based on the acquired information, controlling the integrated valve, controlling the positive pressure pump to drive the liquid in the first liquid chamber to enter the filtering device through the integrated valve, and then flowing into the bioreactor through the integrated valve, and controlling the negative pressure pump to drive the liquid in the bioreactor to enter the second liquid chamber through the integrated valve; and/or controlling the integrated valve, controlling the positive pressure pump to drive the liquid in the second liquid chamber to enter the filtering device through the integrated valve, and then flowing into the bioreactor through the integrated valve, and controlling the negative pressure pump to drive the liquid in the bioreactor to enter the first liquid chamber through the integrated valve.

In some embodiments, the biological filtration system further comprises a processor for: based on the acquired information, controlling the integrated valve, controlling the negative pressure pump to drive the liquid in the bioreactor to enter the filtering device through the integrated valve, then flowing into the second liquid chamber through the integrated valve, controlling the positive pressure pump to drive the liquid in the first liquid chamber to enter the bioreactor through the integrated valve, and/or controlling the integrated valve, controlling the negative pressure pump to drive the liquid in the bioreactor to enter the filtering device through the integrated valve, then flowing into the first liquid chamber through the integrated valve, and controlling the positive pressure pump to drive the liquid in the second liquid chamber to enter the bioreactor through the integrated valve.

In some embodiments, the biological filtration system further comprises a processor for: based on the acquired information, controlling the integrated valve, controlling the positive pressure pump to drive the liquid in the first liquid chamber to enter the filtering device through the integrated valve, then flowing into the bioreactor through the integrated valve, controlling the positive pressure pump to drive the liquid in the second liquid chamber to enter the bioreactor through the integrated valve, and/or controlling the integrated valve, controlling the negative pressure pump to drive the liquid in the bioreactor to enter the filtering device through the integrated valve, then flowing into the second liquid chamber through the integrated valve, and controlling the negative pressure pump to drive the liquid in the bioreactor to enter the first liquid chamber through the integrated valve.

In some embodiments, the biological filtration system further comprises a processor for: based on the acquired information, controlling the integrated valve, controlling the positive pressure pump to drive the liquid in the second liquid chamber to enter the filtering device through the integrated valve, then flowing into the bioreactor through the integrated valve, controlling the positive pressure pump to drive the liquid in the first liquid chamber to enter the bioreactor through the integrated valve, and/or controlling the integrated valve, controlling the negative pressure pump to drive the liquid in the bioreactor to enter the filtering device through the integrated valve, then flowing into the first liquid chamber through the integrated valve, and controlling the negative pressure pump to drive the liquid in the bioreactor to enter the second liquid chamber through the integrated valve.

In some embodiments, the integrated valve comprises a valve body, a fluid inlet and a fluid outlet, a flow passage, and a switch, wherein the fluid inlet and outlet is located on the valve body and the fluid inlet and outlet is in communication with the flow passage; the flow channels are positioned in the valve body, and a plurality of flow channels are communicated to form branches; the switch is connected with the valve body and is movably communicated with the flow channel, and the switch is used for realizing the flow switching of fluid between the switch and the flow channel; the valve body comprises a plurality of transverse planes which are transversely distributed and a plurality of longitudinal planes which are longitudinally distributed, the transverse planes are intersected with the longitudinal planes, the flow channel comprises a plurality of transverse flow channels with flow channel axes distributed on the transverse planes and a plurality of longitudinal flow channels with flow channel axes distributed on the longitudinal planes, and the transverse flow channels are communicated through the switch and/or the longitudinal flow channels.

In some embodiments, the lateral planes include a first lateral plane and a second lateral plane; the transverse flow channels comprise a plurality of first transverse flow channels with flow channel axes distributed in a first transverse plane and a plurality of second transverse flow channels with flow channel axes distributed in a second transverse plane, the flow channel axes of the longitudinal flow channels and the first transverse plane and/or the second transverse plane are at preset angles, and the first transverse flow channels, the second transverse flow channels and the first transverse flow channels and the second transverse flow channels are communicated through the longitudinal flow channels and/or the switches.

Drawings

The present specification will be further elucidated by way of example embodiments, which will be described in detail by means of the accompanying drawings. The embodiments are not limiting, in which like numerals represent like structures, wherein:

FIG. 1 is a schematic diagram of an exemplary biological filtration system according to some embodiments of the present description.

FIG. 2A is a schematic diagram of an exemplary integrated valve according to some embodiments of the present description.

Fig. 2B is a bottom view of an integrated valve according to some embodiments of the present description.

FIG. 2C is a cross-sectional view A-A of FIG. 2B.

Fig. 2D is a cross-sectional view of B-B in fig. 2B.

Fig. 2E is a front view of an integrated valve according to some embodiments of the present description.

Fig. 2F is a cross-sectional view taken along line C-C in fig. 2E.

Fig. 2G is a sectional view of D-D in fig. 2E.

Fig. 2H is a cross-sectional view of E-E in fig. 2E.

Fig. 2I is a simplified diagram of the internal structure of a switch according to some embodiments of the present description.

Fig. 3A and 3B are schematic diagrams of exemplary biological filtration systems according to example 1 of the present disclosure.

Fig. 4A and 4B are schematic diagrams of an exemplary biological filtration system according to embodiment 2 of the present disclosure.

Fig. 5A and 5B are schematic diagrams of an exemplary biological filtration system according to embodiment 3 of the present disclosure.

Fig. 6A and 6B are schematic diagrams of exemplary biological filtration systems according to example 4 of the present disclosure.

FIG. 7 is a graph showing the comparison of the results of protein retention measured using a biofiltration system and an ATF system according to example 5 of the present specification.

In the figure, 100 is a biological filtration system, 110 is a biological reactor, 111 is a first inlet and outlet, 112 is a second inlet and outlet, 120 is a filtration device, 121 is a first inlet and outlet, 122 is a second inlet and outlet, 123 is a third outlet, 130 is a liquid chamber, 131 is a first liquid chamber, 1311 is a first liquid chamber first end, 1312 is a first liquid chamber second end, 132 is a second liquid chamber, 1321 is a second liquid chamber first end, 1322 is a second liquid chamber second end, 140 is a driving device, 141 is a positive pressure pump, 142 is a negative pressure pump, 150 is an integrated valve, 1501 is a valve body, 1502 is a fluid inlet and outlet, 1502-1 is a first fluid inlet and outlet, 1502-2 is a second fluid inlet and outlet, 1502-3 is a third fluid inlet and outlet, 1502-4 is a fourth fluid inlet and outlet, 1502-5 is a fifth fluid inlet and outlet, 1502-6 is a sixth fluid inlet and outlet, 1503 is a flow channel, 1503-1 is a first transverse flow channel, 1503-1-2 is a first transverse flow channel, 1503-1-3 is a first transverse flow channel three, 1503-1-4 is a first transverse flow channel four, 1503-1-5 is a first transverse flow channel five, 1503-1-6 is a first transverse flow channel six, 1503-2 is a second transverse flow channel, 1503-2-1 is a second transverse flow channel one, 1503-2-2 is a second transverse flow channel two, 1503-2-4 is a second transverse flow channel four, 1503-2-5 is a second transverse flow channel five, 1503-2-6 is a second transverse flow channel six, 1503-3 is a longitudinal flow channel, 1504 is a switch, 1504-1 is a first switch, 1504-2 is a second switch, 1504-3 is a third switch, 1504-4 is a fourth switch, 1504-5 is a fifth switch, 1504-6 is a sixth switch, 15041 is a communicating component, 15042 is a blocking component, 160 is a liquid collecting device, 170 is a negative pressure energy storage device, 180 is a liquid level sensor, 190 is a pressure sensor, 1100 is a flow sensor, and 1200 is a metering pump.

Detailed Description

In order to more clearly illustrate the technical solutions of the embodiments of the present specification, the drawings that are required to be used in the description of the embodiments will be briefly described below. It is apparent that the drawings in the following description are only some examples or embodiments of the present specification, and it is possible for those of ordinary skill in the art to apply the present specification to other similar situations according to the drawings without inventive effort. Unless otherwise apparent from the context of the language or otherwise specified, like reference numerals in the figures refer to like structures or operations.

It will be appreciated that "system," "apparatus," "unit" and/or "module" as used herein is one method for distinguishing between different components, elements, parts, portions or assemblies at different levels. However, if other words can achieve the same purpose, the words can be replaced by other expressions.

As used in this specification and the claims, the terms "a," "an," "the," and/or "the" are not specific to a singular, but may include a plurality, unless the context clearly dictates otherwise. In general, the terms "comprises" and "comprising" merely indicate that the steps and elements are explicitly identified, and they do not constitute an exclusive list, as other steps or elements may be included in a method or apparatus.

A flowchart is used in this specification to describe the operations performed by the system according to embodiments of the present specification. It should be appreciated that the preceding or following operations are not necessarily performed in order precisely. Rather, the steps may be processed in reverse order or simultaneously. Also, other operations may be added to or removed from these processes.

In the related art, such as cell culture, a biological filtration 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, a biofiltration system may filter a reaction fluid within a bioreactor, which refers to a fluid that needs to be filtered. The filtered liquid comprises a retention liquid and a penetrating liquid, wherein the retention liquid is blocked by a filtering device in the biological filtering system, the liquid can enter the biological reactor again for filtering, and the penetrating liquid is the liquid penetrating the filtering device in the biological filtering system. Wherein the retentate may be a desired culture solution, the permeate may be a waste liquid, or the retentate may be a waste liquid, and the permeate may be a desired culture solution. In some embodiments, the retentate in the biological filtration system may be discharged into the bioreactor again to form a new reaction solution. For simplicity of description, the reaction solution, the retentate, and the permeate are collectively referred to as a liquid in this specification.

Some embodiments of the present disclosure provide a biological filtration system that includes a bioreactor, a filtration device, a liquid chamber, a drive device, and an integrated valve. The driving device is connected with the liquid chamber and used for providing power for filtering liquid in the bioreactor, and the integrated valve is communicated with the bioreactor, the filtering device and the liquid chamber and used for controlling the liquid to circulate at least two ways among the bioreactor, the filtering device and the liquid chamber so as to filter the liquid in the bioreactor. The integrated valve is communicated with the bioreactor, the filtering device and the liquid chamber, and controls the liquid to circulate at least two between the bioreactor, the filtering device and the liquid chamber, so that the structure of the biological filtering system can be simplified, and at least two different circulating modes can be provided, thereby improving the filtering efficiency.

As shown in fig. 1, the biological filtration system 100 may include a bioreactor 110, a filtration device 120, a liquid chamber 130, a drive device 140, and an integrated valve 150.

Bioreactor 110 may be a vessel for holding or processing a reaction solution that requires filtration. In some embodiments, as shown in fig. 1, the bioreactor 110 may include a first port 111 and a second port 112.

The first port 111 may be an opening for liquid to enter the bioreactor 110 and to exit the bioreactor 110. For example, the first port 111 may be an opening for liquid to enter the bioreactor 110 from the filter device 120 through the integrated valve 150, or for liquid to enter the filter device 120 from the bioreactor 110 through the integrated valve 150. As an example, the liquid in the bioreactor 110 may flow to the filter device 120 via the first inlet and outlet 111 and the integrated valve 150, and the liquid in the filter device 120 may enter the bioreactor 110 via the integrated valve 150 and the first inlet and outlet 111.

The second port 112 may be an opening for liquid to enter the bioreactor 110 and to exit the bioreactor 110. For example, the second port 112 may be an opening for liquid to enter the bioreactor 110 from the liquid chamber 130 through the integrated valve 150, or for liquid to enter the liquid chamber 130 from the bioreactor 110 through the integrated valve 150. As an example, in some embodiments, liquid in the bioreactor 110 may flow to the liquid chamber 130 via the second inlet 112 and the integrated valve 150, and liquid in the liquid chamber 130 may also enter the bioreactor 110 via the integrated valve 150 and the second inlet 112.

The filter device 120 may be a device that selectively separates a liquid based on the physical and/or chemical characteristics of certain components in the liquid. The filter device 120 may be various types of filter devices such as a biofilm filter device, a hollow fiber column filter device, and the like, which is not limited in this specification.

In some embodiments, the filter device 120 may include a first access port 121 and a second access port 122.

The first access port 121 may be an opening for liquid to enter the filter device 120 and to exit the filter device 120. In some embodiments, the liquid in the filter device 120 may flow to the bioreactor 110 or the liquid chamber 130 via the first access port 121 and the integrated valve 150. Liquid in the bioreactor 110 or liquid chamber 130 may also enter the filter device 120 via the integrated valve 150 and the first access port 121. In some embodiments, the first access port 121 may be disposed at a top or bottom end of the filter device 120.

The second access port 122 may be an opening for liquid to enter the filter device 120 and exit the filter device 120. In some embodiments, the liquid in the filter device 120 may flow to the liquid chamber 130 or the bioreactor 110 via the second access port 122 and the integrated valve 150. Liquid from the liquid chamber 130 or the bioreactor 110 may also enter the filter device 120 via the integrated valve 150 and the second access port 122. In some embodiments, the second access port 122 may be disposed opposite the first access port 121. For example, the first access port 121 may be disposed at a top end of the filter device 120 and the second access port 122 may be disposed at a bottom end of the filter device 120.

In some embodiments, the filter device 120 may further include a third outlet 123. The third outlet 123 may be an outlet for discharging liquid (e.g., permeate). In some embodiments, third outlet 123 may be disposed on a side of filter device 120 and in communication with liquid collection device 160 via a conduit. In some embodiments, the liquid collection device 160 may be a device for storing or processing a liquid (e.g., permeate).

In some embodiments, the number of filter devices 120 may include at least one. In some embodiments, the number of filter devices 120 may include at least two, e.g., 2, 3, 4, or 5, etc., to increase the filtration efficiency of the biological filtration system 100. In some embodiments, at least two filter devices 120 may be connected in series, it being understood that a first access port of one of the adjacent two filter devices communicates with a second access port of the other filter device such that liquid may flow through the at least two filter devices connected in series in sequence. For example, the filter device 120 may include a first filter device and a second filter device. The first inlet and outlet port of the first filter device may communicate with the second inlet and outlet port of the second filter device, which may communicate with the bioreactor 110 or the liquid chamber 130 through the integrated valve, and the first inlet and outlet port of the second filter device may communicate with the liquid chamber 130 or the bioreactor 110 through the integrated valve. In some embodiments, at least two filter devices 120 may be connected in parallel, it being understood that liquid flowing through the at least two filter devices may be diverted to each of the at least two filter devices to increase the throughput of the biological filtration system. For example, the filter device 120 may include a first filter device and a second filter device. The first inlet and outlet ports of the first filter device and the first inlet and outlet port of the second filter device may be joined by a conduit to form a first total inlet and outlet port, which may be in communication with the bioreactor 110 or the liquid chamber 130 through an integrated valve. The second inlet and outlet ports of the first filter device and the second inlet and outlet port of the second filter device may be joined by tubing to form a second total inlet and outlet port, which may be in communication with the liquid chamber 130 or the bioreactor 110 through an integrated valve. In addition, when one or more of the at least two filter devices connected in parallel fails (e.g., plugs), the remaining filter devices may still function properly without affecting the operation of the biological filtration system 100.

The liquid chamber 130 may be used to buffer liquid or may be used to provide a buffer space for liquid exiting the filter device 120 and/or the bioreactor 110. In some embodiments, the number of liquid chambers 130 may be at least one. For example, as shown in fig. 1, the number of liquid chambers 130 may be 2, including a first liquid chamber 131 and a second liquid chamber 132. In the present embodiment, the first liquid chamber 131 and the second liquid chamber 132 are interchangeable. Here, the first liquid chamber and the second liquid chamber need to be distinguished for expression.

The first liquid chamber 131 may include a first liquid chamber first end 1311 and a first liquid chamber second end 1312. The first liquid chamber first end 1311 may be in communication with the integrated valve 150. In some embodiments, the first liquid chamber first end 1311 may be connected to the bioreactor 110 (e.g., the second inlet 112) or the filtration device 120 (e.g., the first access port 121 or the second access port 122) through the integrated valve 150. The first liquid chamber second end 1312 may be in communication with the drive device 140.

The second liquid chamber 132 may include a second liquid chamber first end 1321 and a second liquid chamber second end 1322. The second liquid chamber first end 1321 may be in communication with the integrated valve 150. In some embodiments, the second liquid chamber first end 1321 may be connected to the bioreactor 110 (e.g., the second inlet 112) or the filtration device 120 (e.g., the first access port 121 or the second access port 122) through the integrated valve 150. The second liquid chamber second end 1322 may be in communication with the drive device 140.

The drive device 140 may be coupled to the liquid chamber 130 (e.g., the first liquid chamber 131 and the second liquid chamber 132) for driving liquid into and out of the liquid chamber 130, it being understood that the drive device 140 may provide the motive force for the biological filtration system 100 to filter the liquid within the biological reactor 110.

In some embodiments, the driving device 140 may include a positive pressure pump 141 and a negative pressure pump 142.

The positive pressure pump 141 may be a device for pumping gas to the liquid chamber 130 (e.g., the first liquid chamber 131 and/or the second liquid chamber 131). In some embodiments, the positive pressure pump 141 and both the first and second liquid chambers 131, 132 may be in communication via tubing for driving the flow of liquid from the first and/or second liquid chambers 131, 132 to the bioreactor 110 or the filter device 120 via the integrated valve 150. Illustratively, positive pressure pump 141 is capable of pumping gas into first liquid chamber 131 and/or second liquid chamber 132, providing positive pressure to liquid within first liquid chamber 131 and/or second liquid chamber 132 by pumping gas, thereby driving liquid flow from first liquid chamber 131 and/or second liquid chamber 132 through integrated valve 150 to bioreactor 110 or filter device 120.

The negative pressure pump 142 may be a device for pumping gas from the liquid chamber 130 (e.g., the first liquid chamber 131 and/or the second liquid chamber 132). In some embodiments, the negative pressure pump 142 may be in communication with both the first liquid chamber 131 and the second liquid chamber 132 via tubing for driving liquid flow from the bioreactor 110 or the filter device 120 to the first liquid chamber 131 and/or the second liquid chamber 132 via the integrated valve 150. Illustratively, the negative pressure pump 142 is capable of drawing gas from within the first liquid chamber 131 and/or the second liquid chamber 132, providing a negative pressure to the liquid within the first liquid chamber 131 and/or the second liquid chamber 132 by drawing gas, thereby driving the liquid to flow from the bioreactor 110 or the filter device 120 through the integrated valve 150 to the first liquid chamber 131 and/or the second liquid chamber 132.

In some embodiments, as shown in fig. 1, the integrated valve 150 may be in communication with the bioreactor 110, the filtration device 120, and the liquid chambers 130 (e.g., the first liquid chamber 131 and the second liquid chamber 132). In some embodiments, the number of integrated valves 150 may be 1. The relevant description of the integrated valve 150 may be found elsewhere in this specification (e.g., fig. 2A, 2B, and their associated descriptions), and will not be repeated here.

In the embodiment of the present disclosure, a circulation path may refer to a circulation path through which the liquid is filtered through the filtering device 120 during the alternating driving of the positive pressure and the negative pressure by controlling the driving device 140 and the integrated valve 150. In some embodiments, the at least two circulation flows may include at least two independent circulation flow paths. For example, the first circulation path, the second circulation path, the third circulation path, or the fourth circulation path may be used throughout the entire filtration process. In some embodiments, the at least two circulatory flows may also include any combination of at least two circulatory flow paths, for example, any combination of a first circulatory flow path, a second circulatory flow path, a third circulatory flow path, or a fourth circulatory flow path. As an example, during the entire filtration process, a first circulation flow path may be employed in the front portion of the filtration process and a second circulation flow path may be employed in the rear portion. As another example, during the entire filtration process, the second circulation flow path may be employed in the front portion of the filtration process and the first circulation flow path may be employed in the rear portion. As another example, assuming the overall filtration process duration is T, a third circulation flow path may be employed for a 0-1/3T period, a first circulation flow path may be employed for a 1/3T-2/3T period, and a second circulation flow path may be employed for a 2/3T-T period. As another example, assuming the overall filtration process duration is T, a third circulation flow path may be employed for a 0-1/6T period, a fourth circulation flow path may be employed for a 1/6T-1/3T period, a second circulation flow path may be employed for a 1/3T-2/3T period, and a first circulation flow path may be employed for a 2/3T-T period. For the description of the first circulation flow path, the second circulation flow path, the third circulation flow path, or the fourth circulation flow path, reference may be made to other portions of the present specification (e.g., fig. 3A-6A, 3B-6B, and their related descriptions), and the description thereof will not be repeated here.

By controlling the one integrated valve 150, the embodiments of the present disclosure can control at least two circulation paths of the liquid among the bioreactor 110, the filtering device 120 and the liquid chamber 130, not only can simplify the structure of the biological filtering system 100, but also can enable a user to select a suitable circulation path or a combination of at least two circulation paths from the at least two circulation paths according to different requirements (e.g., different properties of the liquid) for filtering, so as to improve the filtering efficiency.

In some embodiments, the biological filtration system 100 may further include a negative pressure accumulator 170 disposed between the negative pressure pump 142 and the liquid chamber 130. In some embodiments, the negative pressure pump 142 may draw gas from the negative pressure storage device 170 to cause the negative pressure storage device 170 to store negative pressure. When the negative pressure energy storage device 170 is released, liquid may be drawn into the liquid chamber 130. Based on the pressure in the negative pressure storage device 170, the suction rate of the liquid into the liquid chamber 130, and the maximum liquid level in the liquid chamber 130, can be determined. That is, by controlling the pressure value within the negative pressure storage device 170 to be higher (or lower), the rate of suction of liquid into the liquid chamber 130 may be controlled to be faster (or slower) and/or the maximum liquid level within the liquid chamber 130 may be controlled to be higher (or lower).

In some embodiments, the negative pressure energy storage device 170 may include a first negative pressure energy storage device and a second negative pressure energy storage device. The first negative pressure storage means may be provided between the negative pressure pump 142 and the first liquid chamber 131. A second negative pressure storage device may be disposed between the negative pressure pump 142 and the second liquid chamber 132. When the first negative pressure energy storage device and/or the second negative pressure energy storage device are released, liquid may be drawn into the first liquid chamber 131 and/or the second liquid chamber 132. Based on the pressure in the first negative pressure energy storage device and/or the second negative pressure energy storage device, the suction speed of the liquid into the first liquid chamber 131 and/or the second liquid chamber 132, and the highest liquid level in the first liquid chamber 131 and/or the second liquid chamber 132 may be determined.

In some embodiments, the biological filtration system 100 may further include a liquid level sensor 180 for monitoring the liquid level within the liquid chamber 130 and/or the biological reactor 110. In some embodiments, when the biological filtration system 100 includes the negative pressure energy storage device 170, a fluid level sensor 180 may be disposed in each of the fluid chambers 130, located at the bottom of the fluid chamber 130, for monitoring the lower fluid level limit of the fluid chamber 130. In some embodiments, when the biological filtration system 100 does not include the negative pressure energy storage device 170, at least two liquid level sensors 180 may be disposed within each liquid chamber 130, at the top and bottom of the liquid chamber 130, respectively, for monitoring the upper and lower liquid level limits of the liquid chamber 130, respectively.

In some embodiments, the level sensor 180 may not be provided within the bioreactor 110 while the level of the liquid within the bioreactor 110 remains balanced (which may also be understood as the level of the liquid is substantially constant).

In some embodiments, the biological filtration system 100 may further include pressure sensors 190 disposed at the first, second, and third outlet ports 121, 122, 123 of the filtration device 120, respectively, for detecting the pressure at the first, second, and third outlet ports 121, 122, 123. By comparing the pressures at the first access port 121, the second access port 122, and the third outlet 123, it can be determined whether a clog is present within the biological filtration system 100 (e.g., the filtration device 120), so that early warning information can be provided to the user. For example, pressure sensor 190 may be disposed in a line between third outlet 123 of filter device 120 and sump device 160 to detect a pressure between filter device 120 and sump device 160, and if pressure sensor 190 detects a pressure greater than a preset pressure threshold, it may indicate that a blockage exists between filter device 120 and sump device 160. For another example, a pressure sensor 190 may be disposed between the second inlet/outlet port 122 of the filter device 120 and the integrated valve 150 to detect a pressure between the second inlet/outlet port 122 and the integrated valve 150, and if the pressure sensor 190 detects a pressure greater than a preset pressure threshold, it indicates that there is a blockage between the filter device 120 and the integrated valve 150.

The preset pressure threshold may be a preset maximum pressure value. In some embodiments, the preset pressure threshold may be determined based on historical data, simulated simulations, and the like.

In some embodiments, the biological filtration system 100 can also include a flow sensor 1100 for detecting the flow of liquid through the biological filtration system 100 (e.g., through the bioreactor 110).

In some embodiments, the flow sensor 1100 may be disposed at the first port 111 or the second port 112 of the bioreactor 110. For example, the flow sensor 1100 may be disposed on a line between the first port 111 or the second port 112 of the bioreactor 110 and the integrated valve 150 to enable detection of the flow of liquid into or out of the bioreactor 110.

In some embodiments, the biological filtration system 100 can also include a metering pump 1200 for controlling the flow of liquid. In some embodiments, metering pump 1200 may include, but is not limited to, a peristaltic pump. In some embodiments, metering pump 1200 may be disposed in a line between third outlet 123 of filter device 120 and sump device 160 for controlling the flow of liquid from filter device 120 to sump device 160. In some embodiments, metering pump 1200 may also be disposed at first port 111 or second port 112 of bioreactor 110 for controlling the flow of liquid to or from biological filtration system 100 (e.g., from bioreactor 110).

In some embodiments, the biological filtration system 100 can also include an interactive component (not shown in FIG. 1) for communicating information with a user. For example, user input instructions (e.g., settings for the flow of liquid, selections or combinations of circulation flow paths, etc. of the biological filtration system 100) may be obtained via the interactive component. For another example, real-time operational information of the biological filtration system 100 (e.g., liquid flow of the biological filtration system 100, liquid level of the liquid chamber 130 or the biological reactor 110, pressure of the negative pressure energy storage device, current circulation flow path, etc.) may be displayed through the interactive assembly.

In some embodiments, the biological filtration system 100 may also include a processor (not shown in fig. 1). The processor may be configured to be in signal communication with various components (e.g., negative pressure storage device, fluid level sensor, pressure sensor, flow sensor, interaction component, etc.) in the biological filtration system 100 to obtain information from the various components and/or to send control instructions to the various components. For example, when the positive pressure pump 141 is operating, the liquid level sensor 180 monitors liquid level information within the liquid chamber 130 and sends it to the processor. The processor receives the liquid level information and determines whether the liquid level information approaches or reaches a lower liquid level limit. If the fluid level information approaches or reaches the lower fluid level limit, the processor may control the positive pressure pump 141 to stop operating and the negative pressure pump 142 to operate. For another example, while the negative pressure pump 142 is operating, the fluid level sensor 180 monitors fluid level information within the fluid chamber 130 and sends it to the processor. The processor receives the liquid level information and determines whether the liquid level information approaches or reaches an upper liquid level limit. If the fluid level information approaches or reaches the upper fluid level limit, the processor may control the negative pressure pump 142 to stop operating and the positive pressure pump 141 to operate.

In some embodiments, the processor may control the integrated valve 150 and the drive device 140 to effect at least two circulation of liquid between the bioreactor 110, the filtration device 120, and the liquid chamber 130 based on the obtained information. The description of the control of the integrated valve 150 and the driving device 140 to achieve at least two circulation flows of the liquid between the bioreactor 110, the filtering device 120 and the liquid chamber 130 may be found in other parts of the description (e.g., fig. 3A-6A, 3B-6B), and will not be repeated here.

In some embodiments, the processor may include a Central Processing Unit (CPU), an Application Specific Integrated Circuit (ASIC), an application specific instruction set processor (ASIP), a physical arithmetic processing unit (PPU), a Digital Signal Processor (DSP), a Field Programmable Gate Array (FPGA), a Programmable Logic Device (PLD), a controller, a microcontroller unit, a Reduced Instruction Set Computer (RISC), a microprocessor, or the like, or any combination thereof.

In some embodiments, the biological filtration system 100 can also include a storage component (not shown in fig. 1). The storage component may store data, instructions, and/or any other information. In some embodiments, the storage component may store data and/or information related to filtering the liquid within the bioreactor 110. For example, the storage component can store data and/or instructions for filtering different liquids using the biological filtration system 100, such as filtered flow rates for the different liquids, circulation flow paths for the different liquids, on-off information for on-off on the integrated valve for the different circulation flow paths, and the like. In some embodiments, the storage component may include a U disk, a removable hard disk, an optical disk, a memory card, etc., or any combination thereof.

In this specification, "connected" or "circulated" may be used interchangeably. Communication or flow-through may refer to a coupling or connection that allows fluid (e.g., gas, liquid) to flow between biological filtration systems 100, including but not limited to a form of connection such as a pipe connection, an interface connection, or a direct connection.

It should be noted that the above description of the biological filtration system 100 is for illustration and description only, and is not intended to limit the scope of applicability of the present disclosure. Various modifications and variations of the biological filtration system 100 will be apparent to those skilled in the art in light of the present description. However, such modifications and variations are still within the scope of the present description.

FIG. 2A is a schematic diagram of an exemplary integrated valve according to some embodiments of the present description. Fig. 2B is a bottom view of an integrated valve according to some embodiments of the present description. FIG. 2C is a cross-sectional view A-A of FIG. 2B. Fig. 2D is a cross-sectional view of B-B in fig. 2B. Fig. 2E is a front view of an integrated valve according to some embodiments of the present description. Fig. 2F is a cross-sectional view taken along line C-C in fig. 2E. Fig. 2G is a sectional view of D-D in fig. 2E. Fig. 2H is a cross-sectional view of E-E in fig. 2E.

As shown in fig. 2A-2H, the integrated valve 150 may include a valve body 1501, a fluid inlet 1502, a flow channel 1503, and a switch 1504.

The valve body 1501 may be a main body structure of the integrated valve 150. The valve body 1501 may be a regular or irregular structure of polyhedrons (e.g., cubes, cuboids), spheres, ellipsoids, etc. The cross-sectional shape of the valve body 1501 may include, but is not limited to, rectangular, triangular, trapezoidal, circular, etc. In some embodiments, the valve body 1501 may be an integrally formed structure or a split structure. For example, the valve body 1501 may be formed by combining multiple layers, or the like.

The valve body 1501 includes a plurality of transverse planes extending transversely and a plurality of longitudinal planes extending longitudinally therein, with the transverse planes intersecting the longitudinal planes. In the present embodiment, a transverse plane may be understood as a plane parallel to the front view of the integrated valve 150 shown in fig. 1. The illustration in fig. 2C and 2D can be understood as two transverse planes of the valve body 1501. In some embodiments, the plurality of transverse planes may be at a predetermined angle, e.g., parallel. The intersection of the transverse plane with the longitudinal plane may be understood as the transverse plane being at a predetermined angle to the longitudinal plane, e.g. 45 °, 90 ° or 1502 °. The illustrations of fig. 2F-2H can be understood as three longitudinal planes of the valve body 1501.

In some embodiments, as shown in fig. 2C-2D, 2F-2H, a flow channel 1503 is provided within the valve body 1501. As shown in fig. 2A-2H, a fluid inlet 1502 is provided on the valve body 1501, and the fluid inlet 1502 communicates with the flow channel 1503. Wherein communication may be understood as two components (e.g., fluid inlet 1502 and fluid channel 1503) being interconnected to form a fluid flow channel.

The fluid inlet 1502 refers to an opening for fluid to flow into the flow channel 1503 and/or out of the flow channel 1503. The number of fluid ports 1502 may be N3, where N3 may be an integer greater than 0. For example, 2, 3, 4, 5, 6, etc. The number of fluid ports 1502 may also be set based on actual requirements.

The fluid inlet 1502 may be regular or irregular in shape, such as tubular, rectangular cavity, etc. In some embodiments, fluid port 1502 may be in communication with a portion of flow channel 1503 within valve body 1501. In some embodiments, fluid port 1502 may be fixedly coupled to valve body 1501. In some embodiments, the fixed connection may include, but is not limited to, threaded connection, adhesive, welding, and the like.

In some embodiments, the flow channel axes of N3 fluid ports 1502 (e.g., first fluid port 1502-1, second fluid port 1502-2, third fluid port 1502-3, fourth fluid port 1502-4, fifth fluid port 1502-5, and sixth fluid port 1502-6, as shown in FIG. 2C) may lie in one lateral plane (e.g., may be referred to as a first lateral plane or a second lateral plane).

The flow channel 1503 refers to a channel for fluid to flow in the valve body 1501. In some embodiments, the number of flow channels 1503 may be based on actual requirements.

The flow channels 1503 may include, but are not limited to, regular or irregular shapes such as tubular, rectangular cavity, and the like. In some embodiments, the cross-section of the flow channel axis of flow channel 1503 may be rectangular in the middle and arcuate at both ends (e.g., hemispherical). Wherein the width of the rectangle may be equal to the diameter of the hemisphere. By designing the two ends of the flow channel 1503 to be arc-shaped (e.g., hemispherical), the fluid can be effectively prevented from forming turbulence at the two ends of the flow channel 1503, and thus the flow resistance of the fluid in the flow channel 1503 can be reduced, and the stability of the integrated valve 150 can be improved.

In some embodiments, the flow channel axes of flow channels 1503 may be distributed in multiple planes.

As shown in fig. 2B-2D, the lateral planes may include a first lateral plane and a second lateral plane. In some embodiments, the first transverse plane and the second transverse plane may be at a predetermined angle (e.g., 0 °, 5 °, 10 °, 15 °, etc.). As an example, the first transverse plane and the second transverse plane may be parallel (i.e., a preset angle of 0 ° or 180 °). As shown in fig. 2C-2D and 2F-2H, the flow channel 1503 may include a plurality of transverse flow channels with flow channel axes distributed on a transverse plane and a plurality of longitudinal flow channels with flow channel axes distributed on a longitudinal plane, where the plurality of transverse flow channels are communicated with each other through a plurality of longitudinal flow channels and/or the switch 1504. For a description of the communication between the plurality of lateral flow channels via the plurality of longitudinal flow channels and/or the switch 1504, reference may be made to other portions of the present disclosure (e.g., fig. 2F-2I and their associated descriptions), which are not repeated herein.

As shown in fig. 2C, the lateral flow channels include a plurality of first lateral flow channels 1503-1 having flow channel axes distributed in a first lateral plane, and the plurality of first lateral flow channels 1503-1 are not directly connected. As shown in fig. 2D, the lateral flow channels further include a plurality of second lateral flow channels 1503-2 having flow channel axes that are distributed in a second lateral plane, and the plurality of second lateral flow channels are not directly connected.

As shown in fig. 2E-2H, the flow channel axis of the longitudinal flow channel forms a preset angle with the first transverse plane and/or the second transverse plane. In some embodiments, the preset angle may be greater than 0 ° and not greater than 90 °, e.g., 30 °, 60 °, 90 °, or the like.

In some embodiments, the plurality of first lateral flow channels 1503-1 are not in direct communication with the plurality of second lateral flow channels 1503-2. The first plurality of lateral flow channels 1503-1, the second plurality of lateral flow channels 1503-2, and the first plurality of lateral flow channels 1503-1 and the second plurality of lateral flow channels 1503-2 are in communication via a plurality of longitudinal flow channels and/or switches 1504.

As shown in fig. 2B-2D, the first and second lateral planes may refer to cross-sections of the integrated valve 150. For example, the first transverse plane may refer to the A-A profile as shown in fig. 2B or fig. 2C, and the second transverse plane may refer to the B-B profile as shown in fig. 2B or fig. 2D. In some embodiments, as shown in FIG. 2C, a first transverse plane may refer to a plane in which the flow channel axes of N3 fluid ports 1502 (e.g., first fluid port 1502-1, second fluid port 1502-2, third fluid port 1502-3, fourth fluid port 1502-4, fifth fluid port 1502-5, and sixth fluid port 1502-6) lie. In some embodiments, the first transverse plane and the second transverse plane may be parallel. In some embodiments, the first transverse plane and the second transverse plane may be at a predetermined angle (e.g., 30 °, 60 °, 90 °, 1502 °, etc.).

It should be noted that the definition of the first transverse plane and the second transverse plane is only for distinguishing the different planes where the flow channel axes of the different flow channels 1503 are located, and the specific positions of the first transverse plane and the second transverse plane are not limited.

The first transverse flow channel 1503-1 may refer to a flow channel having a flow channel axis lying in a first transverse plane. In some embodiments, the number of first lateral flow channels 1503-1 may be M, where M may be an integer greater than 0. For example, 2, 3, 4, 5, 6, etc. The number of first transverse flow channels 1503-1 may be set based on actual requirements. For example, when M is 6, as shown in FIG. 2C, the 6 first lateral runners 1503-1 may include a first lateral runner one 1503-1-1, a first lateral runner two 1503-1-2, a first lateral runner three 1503-1-3, a first lateral runner four 1503-1-4, a first lateral runner five 1503-1-5, and a first lateral runner six 1503-1-6.

In some embodiments, the M first lateral flow channels 1503-1 are not in communication, i.e., the M first lateral flow channels 1503-1 are independent of each other and are not in communication with each other.

The second transverse flow channel 1503-2 refers to a flow channel having a flow channel axis lying in a second transverse plane. In some embodiments, the number of second lateral flow channels 1503-2 may be P, where P may be an integer greater than 0. For example, 2, 3, 4, 5, 6, etc. The number of second transverse flow channels 1503-2 may be set based on actual requirements. For example, when P is 6, as shown in FIG. 2D, the 6 second lateral flow channels 1503-2 may include a second lateral flow channel one 1503-2-1, a second lateral flow channel two 1503-2-2, a second lateral flow channel three 1503-2-3, a second lateral flow channel four 1503-2-4, a second lateral flow channel five 1503-2-5, and a second lateral flow channel six 1503-2-6.

In some embodiments, the P second lateral flow channels 1503-2 are not in communication, i.e., the P second lateral flow channels 1503-2 are independent of each other and are not in communication with each other.

The longitudinal flow channels 1503-3 may refer to flow channels disposed at a predetermined angle to the first and/or second lateral flow channels 1503-1, 1503-2 and communicating with the first and/or second lateral flow channels 1503-1, 1503-2. In some embodiments, the number of longitudinal channels 1503-3 may be Q, where Q may be an integer greater than 0. For example, 2, 3, 4, 5, 6, etc. The number of longitudinal flow channels 1503-3 may be set based on actual requirements.

In some embodiments, the first and second lateral flow channels 1503-1, 1503-2 may communicate through the longitudinal flow channel 1503-3 and/or the switch 1504. For a description of the switch, reference may be made to other parts of the present specification (e.g., fig. 2F-2H and related descriptions thereof), and no further description is given here.

Fluid inlet 1502 may include a first fluid inlet 1502-1, a second fluid inlet 1502-2, a third fluid inlet 1502-3, a fourth fluid inlet 1502-4, a fifth fluid inlet 1502-5, and a sixth fluid inlet 1502-6. Each of the N3 fluid inlets and outlets 1502 communicates with a plurality of first transverse channels 1503-1 having channel axes that are distributed in a first transverse plane or a plurality of second transverse channels 1503-2 having channel axes that are distributed in a second transverse plane, respectively. As shown in fig. 2C, fluid port 1502 may be in communication with first lateral flow channel 1503-1. Illustratively, the first fluid port 1502-1 may be in communication with a first transverse flow channel one 1503-1-1, the second fluid port 1502-2 may be in communication with a first transverse flow channel two 1503-1-2, the third fluid port 1502-3 may be in communication with a first transverse flow channel three 1503-1-3, the fourth fluid port 1502-4 may be in communication with a first transverse flow channel four 1503-1-4, the fifth fluid port 1502-5 may be in communication with a first transverse flow channel five 1503-1-5 and the sixth fluid port 1502-6 may be in communication with a first transverse flow channel six 1503-1-6.

The switch 1504 refers to a component that enables fluid communication switching between the different flow channels 1503. In some embodiments, the number of switches 1504 may be N1, where N1 may be 2, 3, 4, 5, 6, or the like. In some embodiments, the number of switches 1504 may be based on actual needs.

In some embodiments, the switch 1504 may be located on the exterior surface of the valve body 1501 or inside the valve body 1501. The switch 1504 is connected to the valve body 1501 and is in movable communication with the flow channel 1503 for effecting a switching of fluid flow between the switch 1504 and the flow channel 1503. In some embodiments, the switch 1504 and the valve body 1501 may be fixedly attached, such as by adhesive, snap-fit, or the like.

In some embodiments, active communication of switch 1504 with flow channel 1503 may be understood as being in communication/non-communication with flow channel 1503, respectively, based on the on/off state of switch 1504. It will be appreciated that when the switch 1504 is in the on state, the switch 1504 is in communication with the flow channel 1503, and fluid may flow between the switch 1504 and the flow channel 1503, or when the switch 1504 is in the on state, the switch 1504 and the valve body 1501 form a flow space through which at least two flow channels 1503 may communicate. When the switch 1504 is in the off state, the switch 1504 and the flow channel 1503 are in the non-communication state, and fluid cannot flow between the switch 1504 and the flow channel 1503.

In some embodiments, the switch 1504 may be designed in a variety of configurations to enable fluid flow switching between the switch 1504 and the different flow channels 1503. For example, the switch 1504 may be an openable and closable conduit structure such that when the conduit is closed (i.e., the switch is closed), fluid cannot pass between the switch 1504 and the flow channel 1503. When the conduit is on (i.e., the switch is open), fluid may be circulated between the switch 1504 and the flow channel 1503.

As shown in fig. 2F-2H, the switch 1504 may include a communication assembly 15041.

The communication assembly 15041 may be used to communicate at least two of the flow channels 1503 to enable fluid communication between the at least two flow channels 1503. In some embodiments, the communication assembly 15041 and the valve body 1501 may be fixedly attached (e.g., glued, welded, etc.).

In some embodiments, the material of the communication assembly 15041 may be an elastic material. For example, the elastic material may include, but is not limited to, rubber, polyurethane elastomer, and the like.

In some embodiments, the communication assembly 15041 and the valve body 1501 may form a flow space through which at least two flow channels 1503 may communicate. Compared with a switch consisting of a plurality of openable and closable pipelines and valves (whether the valves on the pipelines are required to be opened or closed to realize the circulation between the two flow channels 1503 or not), the operation is more convenient and faster by only controlling the connection and the closure of the circulation space formed by the communication assembly 15041 and the valve body 1501 to realize the circulation between the flow channels 1503 or not. As shown in fig. 2F, when the communication unit 15041 of the switch 1504 is driven to move to the side close to the flow channel 1503 until the flow channel 1503 is blocked (i.e., when the switch is turned off), the communication unit 15041 of the switch 1504 and the valve body 1501 cannot form the flow space S. When the communication assembly 15041 of the drive switch 1504 moves to a side away from the flow channel 1503 (i.e., when the switch is open), the communication assembly 15041 and the valve body 1501 may form a flow space S. As shown in fig. 2F, the second first transverse flow channel 1503-2-1 and the second transverse flow channel 1503-2-2 may communicate through the flow space S and the longitudinal flow channel 1503-3, thereby achieving fluid flow between the second transverse flow channel 1503-2-1 and the second transverse flow channel 1503-2-2. As shown in fig. 2G and 2H, the first and second lateral flow channels 1503-1, 1503-2 may communicate through the longitudinal flow channel 1503-3.

In some embodiments, the switch 1504 may also include a blocking assembly 15042.

The blocking assembly 15042 is an assembly that can be driven to perform the opening and closing functions of the switch 1504. In some embodiments, the occluding component 15042 may be a cylinder, a circular table, or the like.

In some embodiments, the occluding component 15042 and the communicating component 15041 may be of unitary construction, i.e., the occluding component 15042 is integral with the communicating component 15041. In some embodiments, the occluding component 15042 and the communicating component 15041 may also be a split structure. For example, the blocking assembly 15042 and the communication assembly 15041 may be fixedly connected to form the switch 1504.

In some embodiments, the end of the blocking assembly 15042 adjacent to the flow channel 1503 may correspond to the flow channel 1503, and the size of the end of the blocking assembly 15042 adjacent to the flow channel 1503 may match the size of the flow channel 1503. Where the dimensions may refer to diameters or equivalent diameters.

In some embodiments, the end of the blocking assembly 15042 adjacent to the flow channel 1503 corresponding to the flow channel 1503 may be understood as driving the blocking assembly 15042 of the switch 1504 to move to the side adjacent to the flow channel 1503, and the end of the blocking assembly 15042 adjacent to the flow channel 1503 may completely block the flow channel 1503 when the end of the blocking assembly 15042 adjacent to the flow channel 1503 contacts the flow channel 1503.

As shown in fig. 2F-2H, the blocking component 15042 is correspondingly disposed above the flow channel 1503, and the size of the end of the blocking component 15042 close to the flow channel 1503 is equal to the size of the flow channel 1503, when the blocking component 15042 of the driving switch 1504 moves to the side close to the flow channel 1503, the switch 1504 is in a closed state when the end of the blocking component 15042 close to the flow channel 1503 contacts with the flow channel 1503, so as to realize the blocking of the flow channel 1503.

In some embodiments of the present disclosure, the switch is simple in structure, which may enable the integrated valve to be simple in structure and small in size. When the switch is turned on, the communication assembly can form a communication space with the valve body, so that fluid can circulate between the switch and at least two flow channels, and the system structure (for example, pipelines and valves are reduced) can be simplified.

In some embodiments, the integrated valve 150 may also include a driving member (not shown).

The driving part means a part for driving the switch 1504 to perform an opening and closing operation. For example, the drive component may include one or more of a cylinder, an electric cylinder, an electromagnet, a mechanical spring, and the like.

In some embodiments, a drive member may be used to drive the movement of the switch 1504 to effect a switching of fluid flow between the different flow channels 1503. Illustratively, when the driving member is a cylinder, the cylinder may implement the opening and closing control of the switch 1504 by the movement of the piston. When the piston of the cylinder protrudes outward, the drive switch 1504 performs a closing operation. When the piston of the cylinder is contracted inward, the communication assembly 15041 may be restored to the open state by its elastic restoring force. In some embodiments, a drive member may be directly or indirectly coupled to the switch 1504 to drive the switch 1504 to perform an opening and closing operation.

In some embodiments, one drive member may be used to drive one switch 1504, it being understood that the number of drive members may be consistent with the number of switches 1504. In some embodiments, one driving unit may drive and control the N1 switches 1504 at the same time, and perform different driving operations on the N1 switches 1504. For example, the first driving member may drive the first switch 1504-1 off while driving the second switch 1504-2 on, etc.

According to some embodiments of the present disclosure, centralized control over a plurality of switches may be achieved by providing a driving component, so that convenience in use of the integrated valve may be improved.

In some embodiments, the switch 1504 may include N1 switches 1504, the flow channel 1503 and the N1 switches may form N2 branches, and the switch 1504 may be included on each of the N2 branches. Wherein N1 is an integer greater than 0. For example, N1 may be 2, 3, 4, 5, or 6, etc.

As shown in fig. 2I, when N1 is 6, the N1 switches 1504 may include a first switch 1504-1, a second switch 1504-2, a third switch 1504-3, a fourth switch 1504-4, a fifth switch 1504-5, and a sixth switch 1504-6.

In some embodiments, when N2 is 6, the N2 branches may include a first branch, a second branch, a third branch, a fourth branch, a fifth branch, and a sixth branch. The N2 branches may consist of a first lateral flow channel 1503-1, a second lateral flow channel 1503-2, and a longitudinal flow channel 1503-3.

As an example, the first lateral flow channel one 1503-1-1, one of the longitudinal flow channels 1503-3 (e.g., longitudinal flow channel one), the second lateral flow channel one 1503-2-1, the first switch 1504-1, the second lateral flow channel two 1503-2, one of the longitudinal flow channels 1503-3 (e.g., longitudinal flow channel two), and the first lateral flow channel two 1503-1-2 are sequentially communicated to form a first branch. The first lateral flow channel three 1503-1-3, one of the longitudinal flow channels 1503-3 (e.g., longitudinal flow channel three), the second lateral flow channel three 1503-2-3, the second switch 1504-2, the second lateral flow channel four 1503-2-4, one of the longitudinal flow channels 1503-3 (e.g., longitudinal flow channel four) and the first lateral flow channel four 1503-1-4 are sequentially communicated to form a second branch. The first transverse runner five 1503-1-5, one of the longitudinal runners 1503-3 (e.g., longitudinal runner five), the second transverse runner five 1503-2-5, the third switch 1504-3, the second transverse runner six 1503-2-6, one of the longitudinal runners 1503-3 (e.g., longitudinal runner six), and the first transverse runner six 1503-1-6 are sequentially communicated to form a third leg. The first one of the lateral flow channels 1503-1-1, one of the longitudinal flow channels 1503-3 (e.g., longitudinal flow channel one), the second lateral flow channel one 1503-2-1, the fourth switch 1504-4, the second lateral flow channel five 1503-2-5, one of the longitudinal flow channels 1503-3 (e.g., longitudinal flow channel five), and the first lateral flow channel five 1503-1-5 are sequentially communicated to form a fourth leg. The first transverse runner four 1503-1-4, one of the longitudinal runners 1503-3 (e.g., longitudinal runner four), the second transverse runner four 1503-2-4, the fifth switch 1504-5, one of the longitudinal runners 1503-3 (e.g., longitudinal runner two), and the first transverse runner two 1503-1-2 communicate to form a fifth leg. The first transverse runner III 1503-1-3, one of the longitudinal runners 1503-3 (e.g., longitudinal runner III), the sixth switch 1504-6, the second transverse runner six 1503-2-6, one of the longitudinal runners 1503-3 (e.g., longitudinal runner six), and the first transverse runner six 1503-1-6 are in communication in sequence to form a sixth leg.

In some embodiments, the fluid ports 1502 may include N3 fluid ports 1502, with the N3 fluid ports 1502 communicating through N2 branches.

As shown in fig. 2I, the first fluid port 1502-1 communicates with the second fluid port 1502-2 through a first branch a (as shown by a thin solid line in fig. 2I), the third fluid port 1502-3 communicates with the fourth fluid port 1502-4 through a second branch b (as shown by a thin dashed line in fig. 2I), the fifth fluid port 1502-5 communicates with the sixth fluid port 1502-6 through a third branch c (as shown by a dashed line in fig. 2I), the first fluid port 1502-1 communicates with the fifth fluid port 1502-5 through a fourth branch d (as shown by a thick dashed line in fig. 2I), the second fluid port 1502-2 communicates with the fourth fluid port 1502-4 through a fifth branch e (as shown by a two-dot chain line in fig. 2I), and the third fluid port 1502-3 communicates with the sixth fluid port 1502-6 through a sixth branch f (as shown by a thick solid line in fig. 2I).

As shown in fig. 2I, when the first switch 1504-1 is turned on, the fourth switch 1504-4 and the fifth switch 1504-5 are turned off, the first fluid inlet 1502-1 and the second fluid inlet 1502-2 are communicated through the first branch a; when the fifth switch 1504-5 and the sixth switch 1504-6 are closed and the second switch 1504-2 is opened, the third fluid inlet 1502-3 and the fourth fluid inlet 1502-4 are communicated through the second branch b; when the fourth switch 1504-4 is closed and the sixth switch 1504-6 is closed and the third switch 1504-3 is open, the fifth fluid inlet 1502-5 and the sixth fluid inlet 1502-6 are in communication via the third leg c.

As shown in fig. 2I, when the fourth switch 1504-4 is turned on and the first switch 1504-1 is turned off, the first fluid inlet 1502-1 and the fifth fluid inlet 1502-5 are communicated through the fourth branch d; when the fifth switch 1504-5 is turned on and the second switch 1504-2 is turned off, the second fluid inlet 1502-2 and the fourth fluid inlet 1502-4 are communicated through the fifth branch e; when the sixth switch 1504-6 is turned on and the third switch 1504-3 is turned off, the third fluid inlet 1502-3 communicates with the sixth fluid inlet 1502-6 through the sixth branch f.

The six branches may be communicated with the bioreactor 110, the filtering device 120, the first liquid chamber 131 and the second liquid chamber 132, so as to realize circulation of liquid among the bioreactor 110, the filtering device 120, the first liquid chamber 131 and the second liquid chamber 132. For example, the first liquid chamber 131 and the filter device 120 may be communicated through the first branch a, the filter device 120 and the bioreactor 110 may be communicated through the second branch b, the bioreactor 110 and the second liquid chamber 132 may be communicated through the third branch c, the bioreactor 110 and the first liquid chamber 131 may be communicated through the fourth branch d, the filter device 120 and the bioreactor 110 may be communicated through the fifth branch e, and the second liquid chamber 132 and the filter device 120 may be communicated through the sixth branch f.

As shown in fig. 2I, the two ends of the first branch a (or the first fluid inlet 1502-1 and the second fluid inlet 1502-2) are respectively connected to the first end 1311 of the first liquid chamber 131 and the first inlet/outlet 121 of the filtering device 120, the two ends of the second branch b (or the third fluid inlet 1502-3 and the fourth fluid inlet 1502-4) are respectively connected to the second inlet/outlet 122 of the filtering device 120 and the first inlet/outlet 111 of the bioreactor 110, the two ends of the third branch c (or the fifth fluid inlet 1502-5 and the sixth fluid inlet 1502-6) are respectively connected to the second inlet/outlet 112 of the bioreactor 110 and the first end 1321 of the second liquid chamber 132, the two ends of the fourth branch d (or the first fluid inlet 1502-1 and the fifth fluid inlet 1502-5) are respectively connected to the first end 1311 of the first liquid chamber 131 and the second inlet/outlet 112 of the bioreactor 110, the two ends of the fifth branch e (or the second fluid inlet 1502-2 and the fourth fluid inlet 1502-4) are respectively connected to the first inlet/outlet 121 of the filtering device 120 and the first inlet/outlet 121 of the first inlet/outlet 111 of the bioreactor 110 and the second inlet/outlet 132, and the two ends of the fourth branch d (or the first inlet/outlet 1502-1 and the third inlet/outlet 1502-5 and the third inlet/outlet 1502-inlet/outlet 1 and the fourth inlet/outlet 1 of the fourth fluid inlet/outlet) are respectively connected to the first inlet/outlet 132 and the first inlet/outlet 132 of the first inlet/outlet 120 and the first inlet/outlet 1.

In some embodiments, as shown in fig. 2I, each of the branches may include a switch 1504 for enabling the opening and closing of fluid communication on the branch in which the switch 1504 is located. The processor may control the opening and closing of the six switches 1504 on the integrated valve 150 based on the obtained information, so that the liquid passes through the opened branch of the integrated valve 150 to realize the circulation of the liquid or the corresponding circulation flow path.

The biological filtration system of the present specification will be further illustrated by the following examples.

Example 1

In some embodiments, the processor may obtain instructions through components of the biological filtration system 100 (e.g., interactive components, storage components, etc.), control the integrated valve 150 and the drive device 140 to execute the first circulatory flow path. Fig. 3A and 3B are schematic diagrams of exemplary biological filtration systems according to example 1 of the present disclosure.

The first circulation flow path may include a first circulation flow path and a second circulation flow path. As shown in fig. 3A, the processor may control the first switch 1504-1 on the first branch a, the second switch 1504-2 on the second branch b, and the third switch 1504-4 on the third branch c to be turned on, control the fourth switch 1504-4 on the fourth branch d, the fifth switch 1504-5 on the fifth branch e, and the sixth switch 1504-6 on the sixth branch f to be turned off, and control the positive pressure pump 141 to drive the liquid in the first liquid chamber 131 to enter the filter device 120 through the integrated valve 150, filter the liquid through the filter device 120, and then flow into the bioreactor 110 through the integrated valve 150, and simultaneously control the negative pressure pump 142 to drive the liquid in the bioreactor 110 to enter the second liquid chamber 132 through the integrated valve 150. Specifically, the first circulation flow path one includes: the positive pressure pump 141 applies positive pressure to the first liquid chamber 131, and liquid enters the filtering device 120 from the first end 1311 of the first liquid chamber through the first branch a and the first inlet/outlet port 121, is filtered, and enters the bioreactor 110 through the second inlet/outlet port 122, the second branch b and the first inlet/outlet port 111 in sequence. When the negative pressure pump 142 applies negative pressure to the second liquid chamber 132 or the second negative pressure energy storage device is released, liquid in the bioreactor 110 may enter the second liquid chamber 132 via the third branch c and the second liquid chamber first end 1321. A portion of the liquid (e.g., permeate) filtered by filtration device 120 may flow to sump device 160 via third outlet 123. When the liquid level in the first liquid chamber 131 reaches the lower liquid level limit or the liquid level in the second liquid chamber 132 reaches the upper liquid level limit, as shown in fig. 3B, the processor may control the first switch 1504-1 on the first branch a, the second switch 1504-2 on the second branch B, and the third switch 1504-3 on the third branch c to be turned off, control the fourth switch 1504-4 on the fourth branch d, the fifth switch 1504-5 on the fifth branch e, and the sixth switch 1504-6 on the sixth branch f to be turned on, and control the positive pressure pump 141 to drive the liquid in the second liquid chamber 132 to enter the filter device 120 via the integrated valve 150, to flow into the bioreactor 110 via the integrated valve 150 after being filtered by the filter device 120, and control the negative pressure pump 142 to drive the liquid in the bioreactor 110 to enter the first liquid chamber 131 via the integrated valve 150. Specifically, the first circulation path two includes: the positive pressure pump 141 applies positive pressure to the second liquid chamber 132, and the liquid enters the filtering device 120 from the first end 1321 of the second liquid chamber through the sixth branch f and the second inlet/outlet port 122, and the filtered liquid enters the bioreactor 110 through the first inlet/outlet port 122, the fifth branch e and the first inlet/outlet port 111 in sequence. When the negative pressure pump 142 applies a negative pressure to the first liquid chamber 131 or the first negative pressure storage device is released, the liquid in the bioreactor 110 may enter the first liquid chamber 131 via the fourth branch d and the first liquid chamber first end 1311. When the liquid level in the first liquid chamber 131 reaches the upper liquid level limit or the liquid level in the second liquid chamber 132 reaches the lower liquid level limit, the processor controls the integrated valve 150 and the driving device 140 to perform the first circulation path one. The first circulation flow path first and the second circulation flow path second (i.e., the first circulation flow path) are cyclically executed in this order.

In this first circulation flow path, as shown by the arrows in fig. 3A and 3B, the liquid can bidirectionally flush the filter element in the filter device, so that the filter element blockage can be reduced, and the service life of the filter element can be prolonged.

Example 2

In some embodiments, the processor may obtain instructions through components of the biological filtration system 100 (e.g., interactive components, storage components, etc.), control the integrated valve 150 and the drive device 140 to execute the second circulatory flow path. Fig. 4A and 4B are schematic diagrams of an exemplary biological filtration system according to embodiment 2 of the present disclosure.

The second circulation flow path may include a first circulation flow path and a second circulation flow path. As shown in fig. 4A, the processor may control the first switch 1504-1 on the first branch a, the second switch 1504-2 on the second branch b, and the third switch 1504-3 on the third branch c to be turned off, control the fourth switch 1504-4 on the fourth branch d, the fifth switch 1504-5 on the fifth branch e, and the sixth switch 1504-6 on the sixth branch f to be turned on, and control the negative pressure pump 142 to drive the liquid in the bioreactor 110 to enter the filter device 120 through the integrated valve 150, filter the liquid through the filter device 120, and then flow the liquid into the second liquid chamber 132 through the integrated valve 150, and simultaneously control the positive pressure pump 141 to drive the liquid in the first liquid chamber 131 to enter the bioreactor 110 through the integrated valve 150. Specifically, the second circulation flow path one includes: when the negative pressure pump 142 applies negative pressure to the second liquid chamber 132 or the second negative pressure energy storage device is released, the liquid in the bioreactor 110 can enter the filtering device 120 to be filtered through the first inlet and outlet 111, the fifth branch e and the first inlet and outlet port 121 in sequence, and the filtered liquid enters the second liquid chamber 132 through the second inlet and outlet port 122, the sixth branch f and the first end 1321 of the second liquid chamber. The positive pressure pump 141 applies positive pressure to the first liquid chamber 131 and liquid enters the bioreactor 110 from the first liquid chamber first end 1311 via the fourth branch d and the second inlet and outlet 112. A portion of the liquid (e.g., permeate) filtered by filtration device 120 may flow to sump device 160 via third outlet 123. When the liquid level in the first liquid chamber 131 reaches the lower liquid level limit or the liquid level in the second liquid chamber 132 reaches the upper liquid level limit, as shown in fig. 4B, the processor may control the first switch 1504-1 on the first branch a, the second switch 1504-2 on the second branch B, and the third switch 1504-3 on the third branch c to be opened, control the fourth switch 1504-4 on the fourth branch d, the fifth switch 1504-5 on the fifth branch e, and the sixth switch 1504-6 on the sixth branch f to be closed, and control the negative pressure pump 142 to drive the liquid in the bioreactor 110 to enter the filter device 120 through the integrated valve 150, and then flow into the first liquid chamber 131 through the integrated valve 150 after being filtered by the filter device 120, and simultaneously control the positive pressure pump 141 to drive the liquid in the second liquid chamber 132 to enter the bioreactor 110 through the integrated valve 150. Specifically, the second circulation flow path includes: the negative pressure pump 142 applies negative pressure to the first liquid chamber 131, and the liquid enters the filtering device 120 from the bioreactor 110 through the first inlet and outlet 111, the second branch b and the second inlet and outlet port 122 in sequence, and the filtered liquid enters the first liquid chamber 131 through the first inlet and outlet port 121, the first branch a and the first end 1311 of the first liquid chamber in sequence. The positive pressure pump 141 applies positive pressure to the second liquid chamber 132, and liquid in the second liquid chamber 132 may enter the bioreactor 110 via the second liquid chamber first end 1321, the third branch c, and the first inlet/outlet 111. When the liquid level in the first liquid chamber 131 reaches the upper liquid level limit or the liquid level in the second liquid chamber 132 reaches the lower liquid level limit, the processor controls the integrated valve 150 and the driving device 140 to perform the aforementioned second circulation path one. The first and second circulation paths (i.e., the second circulation path) are cyclically executed in this order.

In this second circulation flow path, as shown by the arrows in fig. 4A and 4B, the liquid can bidirectionally flush the filter element in the filter device, so that the filter element blockage can be reduced, and the service life of the filter element can be prolonged.

Example 3

In some embodiments, the processor may obtain instructions through components of the biological filtration system 100 (e.g., interactive components, storage components, etc.), control the integrated valve 150 and the drive device 140 to execute the third circulatory flow path. Fig. 5A and 5B are schematic diagrams of an exemplary biological filtration system according to embodiment 3 of the present disclosure.

The third circulation flow path may include a first third circulation flow path and a second third circulation flow path. As shown in fig. 5A, the processor may control the first switch 1504-1 on the first branch a, the second switch 1504-2 on the second branch b, and the third switch 1504-3 on the third branch c to be turned on, control the fourth switch 1504-4 on the fourth branch d, the fifth switch 1504-5 on the fifth branch e, and the sixth switch 1504-6 on the sixth branch f to be turned off, and control the positive pressure pump 141 to drive the liquid in the first liquid chamber 131 to enter the filter device 120 through the integrated valve 150, filter the liquid through the filter device 120, and then flow into the bioreactor 110 through the integrated valve 150, and simultaneously control the positive pressure pump 141 to drive the liquid in the second liquid chamber 132 to enter the bioreactor 110 through the integrated valve 150. Specifically, the third circulation flow path one includes: the positive pressure pump 141 applies positive pressure to the first liquid chamber 131, and liquid enters the filtering device 120 from the first end 1311 of the first liquid chamber through the first branch a and the first inlet/outlet port 121, is filtered, and enters the bioreactor 110 through the second inlet/outlet port 122, the second branch b and the first inlet/outlet port 111 in sequence. The positive pressure pump 141 applies positive pressure to the second liquid chamber 132, and liquid in the second liquid chamber 132 may enter the bioreactor 110 via the second liquid chamber first end 1321, the third branch c, and the second inlet/outlet 112. A portion of the liquid (e.g., permeate) filtered by filtration device 120 may flow to sump device 160 via third outlet 123. When the liquid level in the first liquid chamber 131 or the second liquid chamber 132 reaches the lower limit of the liquid level, as shown in fig. 5B, the processor may control the first switch 1504-1 on the first branch a, the second switch 1504-2 on the second branch B, and the third switch 1504-3 on the third branch c to be closed, control the fourth switch 1504-4 on the fourth branch d, the fifth switch 1504-5 on the fifth branch e, and the sixth switch 1504-6 on the sixth branch f to be opened, and control the negative pressure pump 141 to drive the liquid in the bioreactor 110 to enter the filter device 120 via the integrated valve 150, filter the liquid through the filter device 120, and then flow the liquid into the second liquid chamber 132 via the integrated valve 150, and simultaneously control the negative pressure pump 142 to drive the liquid in the bioreactor 110 to enter the first liquid chamber 131 via the integrated valve 150. Specifically, the third circulation flow path two includes: when the negative pressure pump 142 applies negative pressure to the second liquid chamber 132 or the second negative pressure energy storage device is released, the liquid enters the filtering device 120 from the bioreactor 110 through the first inlet and outlet 111, the fifth branch e and the first inlet and outlet port 121 in sequence, and the filtered liquid enters the second liquid chamber 132 through the second inlet and outlet port 122, the sixth branch f and the first end 1321 of the second liquid chamber in sequence. When the negative pressure pump 142 applies a negative pressure to the first liquid chamber 131 or the first negative pressure storage device is released, the liquid in the bioreactor 110 may enter the first liquid chamber 131 via the fourth branch d and the first liquid chamber first end 1311. When the liquid level in the first liquid chamber 131 and the second liquid chamber 132 reaches the upper limit of the liquid level, the processor controls the integration valve 150 and the driving device 140 to perform the aforementioned third circulation path one. The first and second (i.e., third) circulation paths are cyclically executed in this order.

Example 4

In some embodiments, the processor may obtain instructions through components of the biological filtration system 100 (e.g., interactive components, storage components, etc.), control the integrated valve 150 and the drive device 140 to execute the fourth circulatory flow path. Fig. 6A and 6B are schematic diagrams of exemplary biological filtration systems according to example 4 of the present disclosure.

The fourth circulation flow path may include a fourth circulation flow path one and a fourth circulation flow path two. As shown in fig. 6A, the processor may control the first switch 1504-1 on the first branch a, the second switch 1504-2 on the second branch b, and the third switch 1504-3 on the third branch c to be turned off, control the fourth switch 1504-4 on the fourth branch d, the fifth switch 1504-5 on the fifth branch e, and the sixth switch 1504-6 on the sixth branch f to be turned on, and control the positive pressure pump 141 to drive the liquid in the second liquid chamber 132 to enter the filter device 120 through the integrated valve 150, filter the liquid through the filter device 120, and then flow into the bioreactor 110 through the integrated valve 150, and simultaneously control the positive pressure pump 141 to drive the liquid in the first liquid chamber 131 to enter the bioreactor 110 through the integrated valve 150. Specifically, the fourth circulation flow path one includes: the positive pressure pump 141 applies positive pressure to the second liquid chamber 132, and the liquid in the second liquid chamber 132 may enter the filtering device 120 to be filtered through the first end 1321 of the second liquid chamber, the second inlet and outlet port 122 and the sixth branch f in sequence, and the filtered liquid enters the bioreactor 110 through the first inlet and outlet port 121, the fifth branch e and the first inlet and outlet port 111. The positive pressure pump 141 applies positive pressure to the first liquid chamber 131 and liquid enters the bioreactor 110 from the first liquid chamber first end 1311 via the fourth branch d and the second inlet and outlet 112. A portion of the liquid (e.g., permeate) filtered by filtration device 120 may flow to sump device 160 via third outlet 123. When the liquid level in the first liquid chamber 131 or the second liquid chamber 132 reaches the lower limit of the liquid level, as shown in fig. 6B, the processor may control the first switch 1504-1 on the first branch a, the second switch 1504-2 on the second branch B, and the third switch 1504-3 on the third branch c to be opened, control the fourth switch 1504-4 on the fourth branch d, the fifth switch 1504-5 on the fifth branch e, and the sixth switch 1504-6 on the sixth branch f to be closed, and control the negative pressure pump 142 to drive the liquid in the bioreactor 110 to enter the filter device 120 through the integrated valve 150, filter the liquid through the filter device 120, and then flow the liquid into the first liquid chamber 131 through the integrated valve 150, and simultaneously control the negative pressure pump 142 to drive the liquid in the bioreactor 110 to enter the second liquid chamber 132 through the integrated valve 150. Specifically, the fourth circulation flow path two includes: when negative pressure is applied to the first liquid chamber 131 by the negative pressure pump 142 or the first negative pressure energy storage device is released, liquid enters the filtering device 120 from the bioreactor 110 through the first inlet and outlet 111, the second branch b and the second inlet and outlet port 122 in sequence, and filtered liquid enters the first liquid chamber 131 through the first inlet and outlet port 121, the first branch a and the first end 1311 of the first liquid chamber in sequence. The negative pressure pump 142 applies a negative pressure to the second liquid chamber 132, and liquid within the bioreactor 110 may enter the second liquid chamber 132 via the second inlet and outlet 112, the third branch c, and the second liquid chamber first end 1321. When the liquid level in the first liquid chamber 131 or the second liquid chamber 132 reaches the upper liquid level limit, the processor controls the integrated valve 150 and the driving device 140 to perform the aforementioned fourth circulation path one. The fourth circulation flow path one and the fourth circulation flow path two (i.e., the fourth circulation flow path) are cyclically executed in this order.

The biological filtration system 100 of the present embodiment may also perform any combination of the aforementioned first, second, third, or fourth circulation flow paths.

Example 5

CHO-k1 cells (purchased from Thermo Fisher SCIENTIFIC) were cultured in the XCELL ATF system of REPLIGEN company in the bioreactor of the biological filtration system 100, respectively. On day 4 of culture, the cell densities all reach 4x 10≡6cells/mL. Culturing for 5 days, and the protein concentration reaches 2g/L-3g/L. The biofiltration system 100 and the ATF system are operated according to the third circulation flow path (or the fourth circulation flow path), respectively, at this time. On day 10 of culture, the cell density reaches 100x 10≡6cells/mL. The cell density is controlled to be 100x 10-6 cells/ml to 120x 10-6 cells/ml and maintained for 35 days. The concentration of protein in the biofiltration system 100 and the ATF system after passing through the filtration device and not passing through the filtration device were measured, respectively, and the protein retention was calculated, and the results are shown in fig. 7. Wherein protein retention = protein concentration of culture broth without passing through the filtration device/protein concentration of culture broth after passing through the filtration device-100%. As shown in fig. 7, the biological filtration system 100 provided in the embodiments of the present disclosure provides a significant improvement in protein retention over the ATF system, and accordingly, can increase the service life of the filter cartridge in the filtration device.

Possible benefits of embodiments of the present description include, but are not limited to: (1) The bioreactor, the filtering device and the liquid chamber (for example, the first liquid chamber and the second liquid chamber) are connected through the integrated valve, so that liquid can be controlled to circulate at least two ways among the bioreactor, the filtering device, the liquid chamber and the integrated valve, the structure of the biological filtering system can be simplified, and a user can select a proper circulation flow path or a combination of at least two circulation flow paths from at least two circulation flow paths according to different requirements (for example, the properties of different liquids) to filter, so that the filtering efficiency is improved; (2) The structure of the integrated valve can be simplified, and the system structure (for example, pipelines and valves are reduced) can be further simplified by realizing the flow switching of the fluid among a plurality of flow channels through the switch; (3) The switch has simple structure, and can lead the structure of the integrated valve to be simple and the volume to be small; (4) The plurality of flow channels positioned in different planes are communicated through the switch, and whether the fluid flows between the different flow channels or not is controlled through the switch, so that the control of the integrated valve can be simpler.

While the basic concepts have been described above, it will be apparent to those skilled in the art that the foregoing detailed disclosure is by way of example only and is not intended to be limiting. Although not explicitly described herein, various modifications, improvements, and adaptations to the present disclosure may occur to one skilled in the art. Such modifications, improvements, and modifications are intended to be suggested within this specification, and therefore, such modifications, improvements, and modifications are intended to be included within the spirit and scope of the exemplary embodiments of the present invention.

Claims

1. A biofiltration system, said system comprising: bioreactor, filtration device, liquid chamber, drive device and integrated valve, wherein,

the driving device is connected with the liquid chamber and is used for providing power for filtering liquid in the bioreactor;

the integrated valve is communicated with the bioreactor, the filtering device and the liquid chamber and is used for controlling the liquid to circulate at least two ways among the bioreactor, the filtering device and the liquid chamber so as to filter the liquid in the bioreactor.

2. The biofiltration system according to claim 1, further comprising a processor for controlling the integrated valve and the driving means to effect at least two circulating fluid flows of liquid between the bioreactor, the filtration means and the liquid chamber based on the acquired information; and/or

The liquid chamber comprises a first liquid chamber and a second liquid chamber; and/or

The integrated valve comprises six branches, and the bioreactor, the filtering device and the liquid chamber are communicated through the six branches so as to realize circulating circulation of liquid among the bioreactor, the filtering device and the liquid chamber; and/or

The integrated valve comprises six branches, and each of the six branches comprises a switch for realizing the opening and closing of the liquid circulation on the branch.

3. The biofiltration system according to claim 1, wherein,

the liquid chamber comprises a first liquid chamber and a second liquid chamber;

the bioreactor comprises a first inlet and a second outlet;

the filtering device comprises a first access port and a second access port;

the first liquid chamber and the second liquid chamber each include a first end;

the integrated valve comprises a first branch, a second branch, a third branch, a fourth branch, a fifth branch and a sixth branch, wherein,

the first end of the first liquid chamber is connected with the first access port through the first branch;

the second access port is connected with the first access port through the second branch;

the second inlet and outlet is connected with the first end of the second liquid chamber through the third branch;

the first end of the first liquid chamber is connected with the second inlet and outlet through the fourth branch;

the first access port is connected with the first inlet and outlet through the fifth branch; and

The first end of the second liquid chamber is connected to the second access port through the sixth branch.

4. The biofiltration system according to claim 1, wherein,

the driving device comprises a positive pressure pump and a negative pressure pump, wherein,

the positive pressure pump is communicated with the first liquid chamber and the second liquid chamber and is used for driving liquid to flow from the first liquid chamber and/or the second liquid chamber to the bioreactor or the filtering device;

the negative pressure pump is communicated with the first liquid chamber and the second liquid chamber and is used for driving liquid to flow from the bioreactor or the filtering device to the first liquid chamber and/or the second liquid chamber.

5. The biofiltration system according to claim 4, further comprising a processor for:

based on the acquired information, controlling the integrated valve, controlling the positive pressure pump to drive the liquid in the first liquid chamber to enter the filtering device through the integrated valve, and then flowing into the bioreactor through the integrated valve, and controlling the negative pressure pump to drive the liquid in the bioreactor to enter the second liquid chamber through the integrated valve; and/or

The integrated valve is controlled, the positive pressure pump is controlled to drive the liquid in the second liquid chamber to enter the filtering device through the integrated valve, then the liquid flows into the bioreactor through the integrated valve, and the negative pressure pump is controlled to drive the liquid in the bioreactor to enter the first liquid chamber through the integrated valve.

6. The biofiltration system according to claim 4, further comprising a processor for:

based on the obtained information, controlling the integrated valve, controlling the negative pressure pump to drive the liquid in the bioreactor to enter the filtering device through the integrated valve, and then flowing into the second liquid chamber through the integrated valve, controlling the positive pressure pump to drive the liquid in the first liquid chamber to enter the bioreactor through the integrated valve, and/or

Controlling the integrated valve, controlling the negative pressure pump to drive liquid in the bioreactor to enter the filtering device through the integrated valve, flowing into the first liquid chamber through the integrated valve, and controlling the positive pressure pump to drive liquid in the second liquid chamber to enter the bioreactor through the integrated valve.

7. The biofiltration system according to claim 4, further comprising a processor for:

based on the obtained information, controlling the integrated valve, controlling the positive pressure pump to drive the liquid in the first liquid chamber to enter the filtering device through the integrated valve, then flowing into the bioreactor through the integrated valve, controlling the positive pressure pump to drive the liquid in the second liquid chamber to enter the bioreactor through the integrated valve, and/or

The integrated valve is controlled, the negative pressure pump is controlled to drive the liquid in the bioreactor to enter the filtering device through the integrated valve, then the liquid flows into the second liquid chamber through the integrated valve, and the negative pressure pump is controlled to drive the liquid in the bioreactor to enter the first liquid chamber through the integrated valve.

8. The biofiltration system according to claim 4, further comprising a processor for:

based on the obtained information, controlling the integrated valve, controlling the positive pressure pump to drive the liquid in the second liquid chamber to enter the filtering device through the integrated valve, then flowing into the bioreactor through the integrated valve, controlling the positive pressure pump to drive the liquid in the first liquid chamber to enter the bioreactor through the integrated valve, and/or

The integrated valve is controlled, the negative pressure pump is controlled to drive the liquid in the bioreactor to enter the filtering device through the integrated valve, then the liquid flows into the first liquid chamber through the integrated valve, and the negative pressure pump is controlled to drive the liquid in the bioreactor to enter the second liquid chamber through the integrated valve.

9. The biofiltration system according to claim 1, wherein,

the integrated valve comprises a valve body, a fluid inlet and outlet, a flow passage and a switch, wherein,

the fluid inlet and outlet are positioned on the valve body and are communicated with the flow channel;

the flow channels are positioned in the valve body, and a plurality of flow channels are communicated to form branches;

the switch is connected with the valve body and is movably communicated with the flow channel, and the switch is used for realizing the flow switching of fluid between the switch and the flow channel;

the valve body comprises a plurality of transverse planes which are transversely distributed and a plurality of longitudinal planes which are longitudinally distributed, the transverse planes are intersected with the longitudinal planes,

the flow channel comprises a plurality of transverse flow channels with flow channel axes distributed on the transverse plane and a plurality of longitudinal flow channels with flow channel axes distributed on the longitudinal plane, and the transverse flow channels are communicated through the switch and/or the longitudinal flow channels.

10. The biological filtration system of claim 9 wherein the lateral planes include a first lateral plane and a second lateral plane; the transverse flow channels comprise a plurality of first transverse flow channels with flow channel axes distributed in a first transverse plane and a plurality of second transverse flow channels with flow channel axes distributed in a second transverse plane, the flow channel axes of the longitudinal flow channels and the first transverse plane and/or the second transverse plane are at preset angles, wherein,

the first transverse flow passages, the second transverse flow passages and the first transverse flow passages and the second transverse flow passages are communicated through the longitudinal flow passages and/or the switches.