Cell culture system

Abstract

The utility model discloses a cell culture system, include: material conveying spare, material conveying spare includes at least two material conveying port and material output port, at least two material conveying port be used for input at least two materials, material output port be used for output material, material distribution spare, material distribution spare includes material input port and at least one material distribution port, material input port with material output port intercommunication is used for receiving the material of material conveying spare output, material distribution port is used for connecting cell factory for providing material for cell factory. According to the cell culture system of utility model embodiment, through pipeline integration, realize cell culture system modularization and standardization, improve the efficiency and effect of cell culture.

Description

Technical Field

[0001] This utility model relates to the field of bioengineering and biopharmaceutical equipment technology, and in particular to a cell culture system. Background Technology

[0002] HEK293 cells (hereinafter referred to as "293 cells") are a "star cell line" in the biopharmaceutical field, possessing characteristics such as efficient expression of exogenous genes, easy adherence and growth, and adaptability to suspension culture. As the biopharmaceutical industry upgrades towards "large-scale, low-cost, and high-stability," traditional small-scale culture methods such as culture dishes and T-flasks can no longer meet the needs of industrial production. Multilayer cell factories (such as 10-layer and 40-layer stacked structures) have gradually become the mainstream culture container for adherent 293 cell culture due to their advantages of "small footprint, large culture area, and relatively simple operation." The culture area of ​​a single 40-layer cell factory can reach more than 2.5㎡, achieving a 293 cell yield of 1.0×10^10. In disposable bioreactors, commonly used disposable fixed-bed bioreactors of 2.4-30㎡ can achieve a cell yield of 2.0×10^10~2.0×10^11 cells, supporting the supply of cell raw materials in pilot-scale and commercial production stages.

[0003] In related technologies, both multilayer cell factories and bioreactors face three major core problems. First, there is a high risk of aseptic failure. The passage process in a 10-layer cell factory inevitably involves open operation, similar to T-flask culture. In contrast, the culture process in a disposable fixed-bed bioreactor involves the complex arrangement of multiple pipelines, including inlet, outlet, sampling port, replenishment tank, and waste tank, requiring proper allocation. Second, there is low operational efficiency. The 10-layer cell factory culture process, which does not use aseptic pipelines, requires open operation in a biosafety cabinet. Third, there is batch-to-batch stability. The operation of a 10-layer cell factory is not standardized enough, and different 10-layer cell factories operated by different personnel can produce batch-to-batch variations in cell quantity and state. Utility Model Content

[0004] One objective of this invention is to propose a cell culture system comprising two parts: a small-scale cell factory and a large-scale bioreactor. Through pipeline integration, the cell culture system is modularized and standardized, thereby improving the efficiency and effectiveness of cell culture.

[0005] A cell culture system according to an embodiment of the present invention includes: a material conveying component, the material conveying component including at least two material conveying ports and a material output port, the at least two material conveying ports being used to input at least two kinds of materials, and the material output port being used to output materials; and a material distributing component, the material distributing component including a material input port and at least one material distributing port, the material input port being connected to the material output port and being used to receive materials output by the material conveying component, and the material distributing port being used to connect to a cell factory to provide materials to the cell factory.

[0006] The cell culture system according to the present invention integrates pipelines to achieve modularization and standardization of the cell culture system, thereby improving the efficiency and effectiveness of cell culture.

[0007] In addition, the cell culture system according to the above embodiments of the present invention may also have the following additional technical features: In some embodiments, the material conveying component includes a first main pipeline and at least two secondary pipelines, with a material conveying port located at one end of the secondary pipelines and the other end of the secondary pipelines connected to the first main pipeline, and the material output port located on the first main pipeline.

[0008] In some embodiments, the first main pipeline includes a first connector, a first connecting pipe, a second connector, a second connecting pipe, a third connector, and a third connecting pipe connected in sequence, and the material outlet is located at the end of the third connecting pipe; The at least two primary pipelines connect the first connector and / or the second connector. The primary pipeline includes a fourth connecting pipe, a fourth connector, and a fifth connecting pipe connected in sequence. The material conveying port is located at the end of the fourth connecting pipe, and the end of the fifth connecting pipe is connected to the first main pipeline.

[0009] In some embodiments, at least one of the first connecting pipe, the second connecting pipe, and the fifth connecting pipe is a flexible hose; and / or, at least one of the first connecting pipe, the second connecting pipe, and the fifth connecting pipe is provided with a corresponding pipe clamp; and / or, at least one of the third connecting pipe and the fourth connecting pipe is a thermoplastic tube; and / or, at least one of the third connecting pipe and the fourth connecting pipe is provided with an air filter at its end; and / or, the first connector is a tee connector; and / or, the second connector is a four-way connector; and / or, the third connector and the fourth connector are two-way connectors.

[0010] In some embodiments, the material distribution component includes a second main pipeline and at least one secondary pipeline, with a material distribution port located at one end of the secondary pipeline and the other end of the secondary pipeline connected to the second main pipeline, and the material input port located on the second main pipeline.

[0011] In some embodiments, the second main pipeline includes a sixth connecting pipe, a sixth connector, a seventh connecting pipe, and a seventh connector connected in sequence, and the material inlet is located at the end of the sixth connecting pipe; The second pipeline includes an eighth connecting pipe, an eighth connector, and a ninth connecting pipe connected in sequence. The eighth connecting pipe is connected to the seventh connector, and the material distribution port is located at the end of the ninth connecting pipe.

[0012] In some embodiments, at least one of the seventh and eighth connecting pipes is a flexible hose; and / or, at least one of the seventh and eighth connecting pipes is provided with a corresponding pipe clamp; and / or, at least one of the sixth and ninth connecting pipes is a thermoplastic tube; and / or, at least one of the sixth and ninth connecting pipes is provided with an air filter at its end; and / or, the seventh connector is a four-way connector; and / or, the sixth and eighth connectors are two-way connectors.

[0013] In some embodiments, the material conveying components are connected as a single unit; and / or, the material dispensing components are connected as a single unit.

[0014] In some embodiments, the cell culture system further includes a drive unit connected to the material conveyor and the material dispenser, and communicating with the material output port and the material input port. The drive unit is used to drive material to flow from the material output port to the material input port. And / or, the material distribution port includes a plurality of ports, which are connected to the material input port, and each material distribution port is adapted to connect to a cell factory; And / or, the at least two material transfer ports are respectively used to connect the culture medium, DPBS, trypsin, and waste bag.

[0015] According to an embodiment of the present invention, the cell culture system further includes a reactor, a third main pipeline, a third secondary pipeline, a sampling pipeline, a liquid replenishment assembly, and an exhaust assembly. The third main pipeline connects the sampling port of the reactor, the third secondary pipeline, the sampling pipeline, and the liquid replenishment assembly. The liquid replenishment assembly connects the liquid outlet of the reactor, the liquid inlet of the reactor, and the third main pipeline. The exhaust assembly connects the gas outlet of the reactor.

[0016] In some embodiments, the third main pipeline further includes a first interface and a second interface, wherein the first interface is configured to connect to the virus solution during the inoculation process, and the second interface is configured to connect to the cell inoculation tank.

[0017] In some embodiments, the third pipeline further includes a seventh interface, an eighth interface, and a ninth interface, wherein the seventh interface is configured to be connected to a waste liquid bag, the eighth interface is configured to be connected to a culture medium storage bag, and the ninth interface is configured to drain the pipeline liquid.

[0018] In some embodiments, the sampling line further includes an eleventh port and a twelfth port, the eleventh port being used for sampling, and the twelfth port being connected to an air filter and used to inject air into the sampling line to drain the liquid in the line.

[0019] In some embodiments, the replenishment assembly includes a replenishment tank, a first connecting pipe, a second connecting pipe, and a third connecting pipe. The first connecting pipe communicates with the upper space within the replenishment tank and is used to connect to the outlet of the reactor. The second connecting pipe communicates with the lower space within the replenishment tank and is used to connect to the inlet of the reactor. The third connecting pipe communicates with the lower space within the replenishment tank and is used to connect to a third main pipeline.

[0020] In some embodiments, the exhaust assembly includes an exhaust canister, a fourth connector, and a fifth connector. The fourth connector communicates with the lower space within the exhaust canister and with the outlet of the reactor. The fifth connector communicates with the upper space of the exhaust canister and is used for exhaust.

[0021] In some embodiments, the third main pipeline is connected as a single unit; And / or, the third pipeline connection is an integral structure; And / or, the sampling pipeline is connected as an integral structure. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the cell culture system of the basic culture section of one embodiment of the present invention.

[0023] Figure 2 This is a schematic diagram of the material conveying component of a cell culture system according to an embodiment of the present invention.

[0024] Figure 3 This is a schematic diagram of the material distribution component of a cell culture system according to an embodiment of the present invention.

[0025] Figure 4 This is a schematic diagram of a cell culture system for the expanded culture portion of another embodiment of the present invention.

[0026] Figure 5 This is a schematic diagram of the third main circuit of a cell culture system according to another embodiment of the present invention.

[0027] Figure 6 This is a schematic diagram of the third pipeline of a cell culture system according to another embodiment of the present invention.

[0028] Figure 7 This is a schematic diagram of the sampling pipeline of a cell culture system according to another embodiment of the present invention.

[0029] Figure 8 This is a schematic diagram of the fluid replenishment component of a cell culture system according to another embodiment of the present invention.

[0030] Figure 9 This is a schematic diagram of the exhaust assembly of a cell culture system according to another embodiment of the present invention.

[0031] Figure label: Cell culture system 1000, material conveyor 111, material conveying ports (1101, 1102, 1103 and 1104), material output port 1105, material distribution unit 112, material input port 1201, material distribution port 1202, first connector 1301, second connector 1302, third connector 1303, fourth connector 1304, sixth connector 1306, seventh connector 1307, eighth connector 1308, tenth connector 1310, eleventh connector 1311, fourteenth connector 1314, fifteenth connector 1315, seventeenth connector 1317, eighteenth connector 1318, twentieth connector 1320, twenty-first connector 1321, and so on. Connector 22 (1322), Connector 24 (1324), Connector 26 (1326), Connector 28 (1328), Connector 30 (1330), Connector 31 (1331), Connector 33 (1333), Connecting Pipe 1 (1401), Connecting Pipe 2 (1402), Connecting Pipe 3 (1403), Connecting Pipe 4 (1404), Connecting Pipe 5 (1405), Connecting Pipe 6 (1406), Connecting Pipe 7 (1407), Connecting Pipe 8 (1408), Connecting Pipe 9 (1409), Connecting Pipe 10 (1410), Connecting Pipe 11 (1411), Connecting Pipe 12 (1412), Connecting Pipe 13 (1413), Connecting Pipe 14 (1414), Connecting Pipe 15 (1415). Sixteenth connecting pipe 1416, seventeenth connecting pipe 1417, eighteenth connecting pipe 1418, nineteenth connecting pipe 1419, twentieth connecting pipe 1420, twenty-first connecting pipe 1421, twenty-second connecting pipe 1422, twenty-third connecting pipe 1423, twenty-fourth connecting pipe 1424, twenty-fifth connecting pipe 1425, twenty-sixth connecting pipe 1426, twenty-seventh connecting pipe 1427, twenty-eighth connecting pipe 1428, twenty-ninth connecting pipe 1429, thirtieth connecting pipe 1430, thirty-first connecting pipe 1431, thirty-second connecting pipe 1432, thirty-third connecting pipe 1433, thirty-fourth connecting pipe 1434, reactor 121, the... Three main pipelines 122, first interface 1601, second interface 1602, third interface 1603, fourth interface 1604, fifth interface 1605, sixth interface 1606, third pipeline 123, seventh interface 1607, eighth interface 1608, ninth interface 1609, tenth interface 1610, sampling pipeline 124, eleventh interface 1611, twelfth interface 1612, thirteenth interface 1613, replenishment assembly 125, replenishment tank 1254, first connecting pipe 1251, second connecting pipe 1252, third connecting pipe 1253, venting assembly 126, venting tank 1266, fourth connecting pipe 1264, fifth connecting pipe 1265, cell factory 2000. Detailed Implementation

[0032] This utility model relates to the field of bioengineering and biopharmaceutical equipment technology, specifically to a tubing connection auxiliary device in the process of large-scale cell culture. It is particularly suitable for the aseptic connection of tubing in HEK293 cell (human embryonic kidney 293 cell) culture systems in multilayer cell factories. It can be widely used in biopharmaceutical scenarios that rely on large-scale HEK293 cell culture, such as the production of viral vector biopharmaceuticals and vaccine development, and provides a technical reference for the design of aseptic connections in cell culture systems.

[0033] In this invention, through the design of aseptic tubing, a highly efficient cell culture tubing connection device is used. After we inoculate 10 layers of cell factory from T bottle, we can use the designed aseptic tubing to ensure that subsequent culture operations are not exposed, greatly reducing the risk of contamination. Even if we operate 3 or 6 10 layers at the same time, we can operate under a Class C cleanroom level.

[0034] The embodiments of this utility model are described in detail below. Examples of these embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain this utility model, and should not be construed as limiting this utility model.

[0035] like Figures 1 to 3 The cell culture system 1000 according to an embodiment of the present invention includes a material conveying component 111 and a material dispensing component 112.

[0036] The material conveying component 111 includes at least two material conveying ports (1101, 1102, 1103, and 1104) and a material output port 1105. The at least two material conveying ports (1101, 1102, 1103, and 1104) are used to input at least two types of materials, and the material output port is used to output materials. The material distributing component 112 includes a material input port 1201 and at least one material distributing port 1202. The material input port 1201 is connected to the material output port 1105 and is used to receive materials output from the material conveying component 111. The material distributing port 1202 is used to connect to the cell factory to provide materials to the cell factory 2000.

[0037] Before setting up a 10-layer cell factory for cell culture, the pre-culture preparation involves preparing the tubing connection components, including a material transfer component 111 and a material dispensing component 112. Following the designed tubing connection, the material transfer component 111 is assembled and placed into a sterile breathing bag, then sterilized using a high-temperature, high-pressure steam sterilizer. Similarly, the material dispensing component 112 is assembled and placed into a sterile breathing bag, also sterilized using a high-temperature, high-pressure steam sterilizer. After sterilization and cooling, the material transfer component 111 is aseptically connected to disposable storage bottles / bags containing culture medium, trypsin, and DPBS (Dulbecco's Phosphate-Buffered Saline) using a sterile connector. The material dispensing component 112 is then aseptically connected to the 10-layer cell factory using the same connector. Finally, the material transfer component 111 and material dispensing component 112 are aseptically connected using the same connector, allowing for efficient and low-risk cell expansion culture using this cell culture tubing connection device.

[0038] According to the embodiment of the present invention, the cell culture system 1000 can input multiple materials through at least two material transfer ports and deliver them to the material distribution unit 112 through the material output port 1105. Subsequently, the material distribution unit 112 can distribute the materials to multiple cell factories for cell culture. This cell culture pipeline connection device can be used for efficient and low-risk cell expansion culture.

[0039] The components of the cell culture tubing connection device are explained in detail below.

[0040] Combination Figure 1 and Figure 2 In some embodiments, the material conveying component 111 includes a first main pipeline and at least two secondary pipelines. A material conveying port is located at one end of a secondary pipeline, and the other end of the secondary pipeline is connected to the first main pipeline. A material output port 1105 is located on the first main pipeline. Different components can be connected using at least two secondary pipelines, simplifying the structure of the cell culture system 1000 and facilitating the connection of the cell culture system 1000 with other components.

[0041] Of course, multiple material conveying ports (1101, 1102, 1103, and 1104) can also be set through a single primary pipeline. This utility model is mainly described using the example of a material conveying component 111 including at least two primary pipelines, which is not intended to limit the scope of protection of this utility model.

[0042] like Figure 2The first main pipeline includes a first connector 1301, a first connecting pipe 1401, a second connector 1302, a second connecting pipe 1402, a third connector 1303, and a third connecting pipe 1403 connected in sequence. A material outlet 1105 is located at the end of the third connecting pipe 1403. Both the first connector 1301 and the second connector 1302 can be used to connect to the first pipeline, which simplifies the structure of the cell culture system and facilitates pipeline connection.

[0043] like Figure 2 At least two primary conduits connect the first connector 1301 and / or the second connector 1302, including but not limited to: all primary conduits are connected to the first connector 1301; or, all primary conduits are connected to the second connector 1302; or, a portion of at least two primary conduits connects to the first connector 1301 and another portion connects to the second connector 1302.

[0044] The first pipeline includes a fourth connecting pipe 1404, a fourth connector 1304, and a fifth connecting pipe 1405 connected in sequence. The fifth connecting pipe 1405 is connected to the first main pipeline. The material conveying port is located at the end of the fourth connecting pipe 1404, and the end of the fifth connecting pipe 1405 is connected to the first main pipeline. This facilitates the connection between the first pipeline and the first main pipeline.

[0045] Optionally, at least one of the first connecting pipe 1401, the second connecting pipe 1402, and the fifth connecting pipe 1405 is a flexible hose. Optionally, at least one of the first connecting pipe 1401, the second connecting pipe 1402, and the fifth connecting pipe 1405 is provided with a corresponding pipe clamp 1501. Optionally, at least one of the third connecting pipe 1403 and the fourth connecting pipe 1404 is a thermoplastic tube. Optionally, at least one end of the third connecting pipe 1403 and the fourth connecting pipe 1404 is provided with an air filter 1502. Optionally, the first connector 1301 is a tee connector. Optionally, the second connector 1302 is a four-way connector. Optionally, the third connector 1303 and the fourth connector 1304 are two-way connectors. In addition, the first connector 1301 can be a Y-type tee connector, and the second connector 1302 can be a cross-shaped four-way connector. Materials can be input into the corresponding primary pipelines through material conveying ports (1101, 1102, 1103) and output from the primary main pipeline. The primary pipeline includes a hose and a pipe clamp 1501, which can conveniently control the flow rate of materials conveyed by the primary pipeline and the primary main pipeline, and can convey materials to the material distribution unit 112.

[0046] See attached document Figure 2The first main pipeline, from end A to end B, consists of a first connector 1301, a first connecting pipe 1401, a second connector 1302, a second connecting pipe 1402, a third connector 1303, a third connecting pipe 1403, and an air filter 1502. In addition, pipe clamps 1501 can be installed on the first connecting pipe 1401, the second connecting pipe 1402, and the fifth connecting pipe 1405. The pipe clamps 1501 can be 7 / 16-inch Robert clamps for controlling the flow rate.

[0047] For example, such as Figure 2 The first main pipeline, from end A to end B, consists of a 1 / 4×7 / 16 inch Y-type tee connector, a 10cm 1 / 4×7 / 16 inch silicone tube, a 7 / 16 inch Robert clamp, a cross-shaped four-way connector, a 50cm 1 / 4×7 / 16 inch silicone tube, a 1 / 4×7 / 16 inch two-way connector, a 30cm thermoplastic tube, and a 0.22μm air filter.

[0048] The primary piping can include four sections, two of which are connected to the first connector 1301, and the other two are connected to the second connector 1302. Each of the four primary piping sections includes, from end A to end B, an air filter 1502, a fourth connecting pipe 1404, a fourth connector 1304, and a fifth connecting pipe 1405. The fifth connecting pipe 1405 can be fitted with a pipe clamp 1501, which can be a 7 / 16-inch Robert clamp, for controlling flow rate.

[0049] For example, Figure 2 The first to fourth primary pipelines from left to right include: The first initial tubing, from end A to end B, consists of a 0.22μm air filter, a 30cm thermoplastic tube, a 1 / 4×7 / 16 inch double connector, a 40cm 1 / 4×7 / 16 inch silicone tube, and a 7 / 16 inch Robert clamp. The second initial tubing, from end A to end B, consists of a 0.22μm air filter, a 30cm thermoplastic tube, a 1 / 4×7 / 16 inch double connector, a 20cm 1 / 4×7 / 16 inch silicone tube, and a 7 / 16 inch Robert clamp. The third first-run tubing, from end A to end B, consists of a 0.22μm air filter, a 30cm thermoplastic tube, a 1 / 4×7 / 16 inch double connector, a 20cm 1 / 4×7 / 16 inch silicone tube, and a 7 / 16 inch Robert clamp. The fourth first-stage tubing, from end A to end B, consists of a 0.22μm air filter, a 30cm thermoplastic tube, a 1 / 4×7 / 16 inch double connector, a 40cm 1 / 4×7 / 16 inch silicone tube, and a 7 / 16 inch Robert clamp.

[0050] Combination Figure 1 and Figure 3 In some embodiments, the material distribution component 112 includes a second main pipeline and at least one secondary pipeline. A material distribution port 1202 is located at one end of the secondary pipeline, and the other end of the secondary pipeline is connected to the second main pipeline. A material input port 1201 is located on the second main pipeline. The secondary pipeline can be used to connect the cell factory 2000, simplifying the structure of the cell culture system 1000 and facilitating the connection of the cell culture system 1000 with other components.

[0051] The second main pipeline includes a sixth connecting pipe 1406, a sixth connector 1306, a seventh connecting pipe 1407 and a seventh connector 1307 connected in sequence, with a material inlet 1201 located at the end of the sixth connecting pipe 1406.

[0052] The second pipeline includes an eighth connecting pipe 1408, an eighth connector 1308, and a ninth connecting pipe 1409 connected in sequence. The eighth connecting pipe 1408 is connected to the seventh connector 1307, and the material distribution port 1202 is located at the end of the ninth connecting pipe 1409.

[0053] Optionally, at least one of the seventh connecting pipe 1407 and the eighth connecting pipe 1408 is a flexible hose. Optionally, at least one of the seventh connecting pipe 1407 and the eighth connecting pipe 1408 is provided with a corresponding pipe clamp 1501. Optionally, at least one of the sixth connecting pipe 1406 and the ninth connecting pipe 1409 is a thermoplastic tube. Optionally, at least one end of the sixth connecting pipe 1406 and the ninth connecting pipe 1409 is provided with an air filter 1502. Optionally, the seventh connector 1307 is a four-way connector; and / or, the sixth connector 1306 and the eighth connector 1308 are two-way connectors.

[0054] The second main pipeline includes an air filter 1502, a sixth connecting pipe 1406, a sixth connector 1306, a seventh connecting pipe 1407, and a seventh connector 1307 connected in sequence. The seventh connecting pipe 1407 is provided with a pipe clamp 1501.

[0055] like Figure 3 The second main pipeline, from end C to end D, consists of an air filter 1502, a sixth connecting pipe 1406, a sixth connector 1306, a seventh connecting pipe 1407, and a seventh connector 1307. Additionally, the seventh connecting pipe 1407 is equipped with a pipe clamp 1501.

[0056] For example, such as Figure 3 The second main pipeline, from end C to end D, consists of a 0.22μm air filter, a 30cm thermoplastic tube, a 1 / 4×7 / 16 inch double connector, a 40cm 1 / 4×7 / 16 inch silicone tube, a 7 / 16 inch Robert clamp, and a cross-shaped four-way connector.

[0057] Optionally, the secondary pipeline may include one or more. Each secondary pipeline can be connected to a cell factory 2000. Air filters 1502 can be correspondingly installed at the material transfer ports (e.g., 1101, 1102, 1103, and 1104), material output port 1105, material input port 1201, and material distribution port 1202. The secondary pipeline includes an eighth connecting pipe 1408, an eighth connector 1308, a ninth connecting pipe 1409, and an air filter 1502 connected in sequence. The eighth connecting pipe 1408 is connected to the seventh connector 1307, and is equipped with a pipe clamp 1501. The eighth connecting pipe 1408 is connected to the second main pipeline.

[0058] Optionally, the secondary pipeline includes three sections, which are respectively connected to the remaining three interfaces of the seventh connector 1307. Each secondary pipeline includes, from end C to end D, an eighth connecting pipe 1408, an eighth connector 1308, a ninth connecting pipe 1409, and an air filter 1502. In addition, the eighth connecting pipe 1408 is provided with a pipe clamp 1501.

[0059] For example, Figure 3 The first to third second-stage pipelines from left to right include: The first and second tubing, from end C to end D, consist of a 40cm 1 / 4×7 / 16 inch silicone tube, a 7 / 16 inch Robert clamp, a 1 / 4×7 / 16 inch double connector, a 30cm 1 / 4×7 / 16 inch thermoplastic tube, and a 0.22μm air filter. The second secondary tubing, from end C to end D, consists of a 40cm 1 / 4×7 / 16 inch silicone tube, a 7 / 16 inch Robert clamp, a 1 / 4×7 / 16 inch double connector, a 30cm 1 / 4×7 / 16 inch thermoplastic tube, and a 0.22μm air filter. The third secondary tubing, from end C to end D, consists of a 40cm 1 / 4×7 / 16 inch silicone tube, a 7 / 16 inch Robert clamp, a 1 / 4×7 / 16 inch double connector, a 30cm 1 / 4×7 / 16 inch thermoplastic tube, and a 0.22μm air filter.

[0060] Optionally, the material conveying component 111 can be connected as a single unit, allowing for assembly, sterilization, and encapsulation. This improves assembly efficiency and facilitates sterilization. Additionally, the material dispensing component 112 can also be connected as a single unit.

[0061] like Figure 1In some embodiments, the cell culture system 1000 further includes a drive unit 113, which is connected to the material conveyor 111 and the material distributor 112, and is connected to the material output port 1105 and the material input port 1201. The drive unit 113 is used to drive the material to flow from the material output port 1105 to the material input port 1201.

[0062] Among them, after the material conveying component 111 and the material distributing component 112 are sterilized in a high-temperature and high-pressure steam sterilizer, they are taken out from the sterilization breathing bag. Figure 2 The 1 / 4 × 7 / 16 inch thermoplastic tube at end B of the material conveyor 111 and Figure 3 The 1 / 4 × 7 / 16 inch thermoplastic tubing at end C of the material distribution unit 112 is connected using a sterile connection machine. For example... Figure 1 As shown.

[0063] In addition, there are multiple material distribution ports 1202, which are connected to the material input port 1201. Each material distribution port 1202 is suitable for connecting to a cell factory.

[0064] Optionally, at least two material transfer ports are used to connect the culture medium, DPBS, trypsin, and waste bag, respectively. Specifically, as... Figure 1 Material transfer port 1101 is connected to culture medium; material transfer port 1102 is connected to DPBS; material transfer port 1103 is connected to trypsin; material transfer port 1104 is connected to waste liquid bag.

[0065] After connecting ends B and C, a sterile connector (including drive unit 113) is added in the middle. Drive unit 113 can be a peristaltic pump. Material transfer ports 1101, 1102, 1103, and 1104 at end A are respectively connected to "culture medium", "DPBS", "trypsin", and "waste bag". Material dispensing port 1202 at end D is connected to 10-layer cell factories. For example, each tube at end D can simultaneously operate 3 10-layer cell factories and passage to 9 10-layer cell factories.

[0066] In addition, such as Figure 4 The present invention also provides a cell culture system 1000, which further includes a reactor 121, a third main pipeline 122, a third pipeline 123, a sampling pipeline 124, a liquid replenishment component 125, and an exhaust component 126. The third main pipeline 122 is connected to the sampling port of the reactor 121, the third pipeline 123, the sampling pipeline 124, and the liquid replenishment component 125. The liquid replenishment component 125 is connected to the liquid outlet of the reactor 121, the liquid inlet of the reactor 121, and the third main pipeline 122. The exhaust component 126 is connected to the gas outlet of the reactor 121.

[0067] The cell culture system 1000 according to this embodiment of the present invention can perform sampling, replenishment, and venting actions using the reactor 121, the third main pipeline 122, the third pipeline 123, the sampling pipeline 124, the replenishment component 125, and the venting component 126, facilitating the stable operation of the reactor 121. This cell culture pipeline connection device can be used for efficient and low-risk cell expansion culture.

[0068] Before conducting cell culture in the disposable fixed-bed bioreactor 121, the components for connecting the pipelines are prepared during the pre-culture preparation work. These components may include the aforementioned third main pipeline 122, third pipeline 123, sampling pipeline 124, replenishment component 125, and exhaust component 126. After assembling the third main pipeline 122, third pipeline 123, sampling pipeline 124, replenishment component 125, and exhaust component 126 according to the designed pipeline connection device, they are respectively placed into sterilization breathing bags and sterilized in a high-temperature and high-pressure steam sterilizer.

[0069] like Figure 5 The third main pipeline 122 includes a first interface 1601, a second interface 1602, a third interface 1603, a fourth interface 1604, a fifth interface 1605, and a sixth interface 1606. The first interface 1601 is configured to connect to the virus solution during the inoculation process; the second interface 1602 is configured to connect to the cell inoculation tank; the third interface 1603 is used to connect to the third pipeline 123 to transfer the culture medium from the 50L storage bag upwards (including the reactor 121 and the replenishment component 125); the fourth interface 1604 is used to connect to the inlet of the replenishment component 125; the fifth interface 1605 is used to connect to the sampling pipeline 124; and the sixth interface 1606 is used to connect to the sampling port of the reactor 121.

[0070] Among them, such as Figure 5The third main pipeline 122 may include the tenth connecting pipe 1410, the tenth connector 1310, the eleventh connecting pipe 1411, the eleventh connector 1311, the twelfth connecting pipe 1412, the thirteenth connecting pipe 1413, the fourteenth connecting pipe 1414, the fourteenth connector 1314, the fifteenth connecting pipe 1415, the fifteenth connector 1315, the sixteenth connecting pipe 1416, the seventeenth connecting pipe 1417, the seventeenth connector 1317, the eighteenth connecting pipe 1418, the eighteenth connector 1318, the nineteenth connecting pipe 1419, the twentieth connecting pipe 1420, the twentieth connector 1320, and the twenty-first connecting pipe 1421. The first interface 1601 is located in the twelfth connecting pipe 1412, the second interface 1602 is located in the twenty-first connecting pipe 1421, the third interface 1603 is located in the nineteenth connecting pipe 1419, the fourth interface 1604 is located in the sixteenth connecting pipe 1416, the fifth interface 1605 is located in the thirteenth connecting pipe 1413, and the sixth interface 1606 is located in the tenth connecting pipe 1410.

[0071] The tenth connecting pipe 1410, the tenth connector 1310, the eleventh connecting pipe 1411, and the eleventh connector 1311 are connected sequentially; the eleventh connector 1311 can be a four-way connector. The twelfth connecting pipe 1412, the thirteenth connecting pipe 1413, and the fourteenth connecting pipe 1414 connect to the other interfaces of the eleventh connector 1311; the other end of the fourteenth connecting pipe 1414 connects to the fourteenth connector 1314, which can be a three-way connector. The fifteenth connecting pipe 1415 and the seventeenth connecting pipe 1417 connect to the other interfaces of the fourteenth connector 1314. The fifteenth connecting pipe 1415, the fifteenth connector 1315, and the sixteenth connecting pipe 1416 are connected in sequence; the other end of the seventeenth connecting pipe 1417 is connected to the seventeenth connector 1317, which can be a tee connector; the eighteenth connecting pipe 1418 and the twentieth connecting pipe 1420 are connected to other interfaces of the seventeenth connector 1317; the eighteenth connecting pipe 1418, the eighteenth connector 1318, and the nineteenth connecting pipe 1419 are connected in sequence; the twentieth connecting pipe 1420, the twentieth connector 1320, and the twenty-first connecting pipe 1421 are connected in sequence.

[0072] Optionally, at least one of the eleventh connecting pipe 1411, the fourteenth connecting pipe 1414, the fifteenth connecting pipe 1415, the seventeenth connecting pipe 1417, the eighteenth connecting pipe 1418, and the twentieth connecting pipe 1420 is a flexible hose. Optionally, at least one of the eleventh connecting pipe 1411, the fourteenth connecting pipe 1414, the fifteenth connecting pipe 1415, the seventeenth connecting pipe 1417, the eighteenth connecting pipe 1418, and the twentieth connecting pipe 1420 is provided with a corresponding pipe clamp 1501. Optionally, at least one of the tenth connecting pipe 1410, the twelfth connecting pipe 1412, the thirteenth connecting pipe 1413, the sixteenth connecting pipe 1416, the nineteenth connecting pipe 1419, and the twenty-first connecting pipe 1421 is a thermoplastic pipe. Optionally, at least one end of the tenth connecting pipe 1410, the twelfth connecting pipe 1412, the thirteenth connecting pipe 1413, the sixteenth connecting pipe 1416, the nineteenth connecting pipe 1419, and the twenty-first connecting pipe 1421 is provided with an air filter 1502 (0.22μm air filter). Optionally, the fourteenth connector 1314 and the seventeenth connector 1317 are tee connectors. Optionally, the eleventh connector 1311 is a four-way connector. Optionally, the tenth connector 1310, the fifteenth connector 1315, the eighteenth connector 1318, and the twentieth connector 1320 are two-way connectors. Additionally, the fourteenth connector 1314 and the seventeenth connector 1317 can be Y-type tee connectors, and the eleventh connector 1311 can be a cross-shaped four-way connector. This allows for convenient control of the flow rate of materials conveyed in the third main pipeline, facilitating material conveying.

[0073] like Figure 5 As shown, the connections from end E to end F are as follows: 10th connecting pipe 1410 (20cm 1 / 4×7 / 16 inch thermoplastic tubing), 10th connector 1310 (1 / 4×7 / 16 inch double connector), 11th connecting pipe 1411 (20cm 1 / 4×7 / 16 inch silicone tubing), 11th connector 1311, 12th connecting pipe 1412, 13th connecting pipe 1413, 14th connecting pipe 1414, 14th connector 1314, 15th connecting pipe 1415, 15th connector 1315, 16th connecting pipe 1416, 17th connecting pipe 1417, 17th connector 1317, 18th connecting pipe 1418, 18th connector 1318, 19th connecting pipe 1419, 20th connecting pipe 1420, 20th connector 1320, and 21st connecting pipe 1421.

[0074] like Figure 5As shown, the connections of the third main pipeline from end E to end F are as follows: 0.22μm air filter - 20cm 1 / 4×7 / 16 inch thermoplastic tubing - 1 / 4×7 / 16 inch double connector - 20cm 1 / 4×7 / 16 inch silicone tubing - 7 / 16 inch Robert clamp - "+" type four connector - two 20cm 1 / 4×7 / 16 inch thermoplastic tubing (+0.22μm air filter) - 20cm 1 / 4×7 / 16 inch silicone tubing - 1 / 4×7 / 16 inch "Y" type three connector - 20cm 1 / 4×7 / 16 inch silicone tubing (another branch connects to 20cm 1 / 4×7 / 16 inch silicone tubing - 7 / 16-inch Robert clamp - 1 / 4×7 / 16-inch double connector - 20cm 1 / 4×7 / 16-inch thermoplastic tubing - 0.22μm air filter) - 1 / 4×7 / 16-inch "Y" tee connector - 20cm 1 / 4×7 / 16-inch silicone tubing (another branch connects to 20cm 1 / 4×7 / 16-inch silicone tubing - 7 / 16-inch Robert clamp - 1 / 4×7 / 16-inch double connector - 20cm 1 / 4×7 / 16-inch thermoplastic tubing - 0.22μm air filter) - 1 / 4×7 / 16-inch double connector - 20cm 1 / 4×7 / 16-inch thermoplastic tubing - 0.22μm air filter.

[0075] like Figure 6 The third pipeline 123 also includes a seventh interface 1607, an eighth interface 1608, a ninth interface 1609, and a tenth interface 1610. The seventh interface 1607 is configured to be connected to the waste liquid bag, and the waste liquid in the replenishment component 125 and the waste liquid in the reactor 121 are discharged to this point. The eighth interface 1608 is configured to be connected to the culture medium storage bag. The ninth interface 1609 is configured to be used to drain the pipeline liquid. The tenth interface 1610 is configured to be connected to the third main pipeline.

[0076] The third conduit 123 includes the twenty-first connector 1321, the twenty-second connecting pipe 1422, the twenty-third connecting pipe 1423, the twenty-fourth connecting pipe 1424, the twenty-fourth connector 1324, the twenty-fifth connecting pipe 1425, the twenty-sixth connecting pipe 1426, the twenty-sixth connector 1326, the twenty-seventh connecting pipe 1427, the twenty-eighth connecting pipe 1428, the twenty-eighth connector 1328, and the twenty-ninth connecting pipe 1429. The twenty-second connecting pipe 1422, the twenty-fourth connecting pipe 1424, the twenty-sixth connector 1326, and the twenty-eighth connecting pipe 1428 are connected to the twenty-first connector 1321; the twenty-second connecting pipe 1422... The 22nd connector 1322 and the 23rd connecting pipe 1423 are connected in sequence, and the 7th interface 1607 is located on the 23rd connecting pipe 1423; the 24th connecting pipe 1424, the 24th connector 1324, and the 25th connecting pipe 1425 are connected in sequence, and the 8th interface 1608 is located on the 25th connecting pipe 1425; the 26th connecting pipe 1426, the 26th connector 1326, and the 27th connecting pipe 1427 are connected in sequence, and the 9th interface 1609 is located on the 27th connecting pipe 1427; the 28th connecting pipe 1428, the 28th connector 1328, and the 29th connecting pipe 1429 are connected in sequence, and the 10th interface 1610 is located on the 29th connecting pipe 1429.

[0077] Optionally, at least one of the twenty-second connecting pipe 1422, the twenty-fourth connecting pipe 1424, the twenty-sixth connector 1326, and the twenty-eighth connecting pipe 1428 is a flexible tube (e.g., a 20cm 1 / 4×7 / 16 inch silicone tube). Optionally, at least one of the twenty-second connecting pipe 1422, the twenty-fourth connecting pipe 1424, the twenty-sixth connector 1326, and the twenty-eighth connecting pipe 1428 is provided with a corresponding pipe clamp 1501 (e.g., a 7 / 16 inch Robert clamp). Optionally, at least one of the twenty-third connecting pipe 1423, the twenty-fifth connecting pipe 1425, the twenty-seventh connector, and the twenty-ninth connecting pipe 1429 is a thermoplastic tube (e.g., a 20cm 1 / 4×7 / 16 inch thermoplastic tube). Optionally, at least one of the twenty-third connecting pipe 1423, the twenty-fifth connecting pipe 1425, the twenty-seventh connecting pipe 1427, and the twenty-ninth connecting pipe 1429 is provided with an air filter 1502 (e.g., a 0.22μm air filter) at its end. Optionally, connector 1321 is a four-way connector (e.g., a cross-shaped four-way connector). Optionally, connectors 1322, 1324, 1326, and 1328 are two-way connectors (e.g., 1 / 4 x 7 / 16 inch two-way connectors). Additionally, connector 1321 can be a cross-shaped four-way connector.

[0078] As shown in Figure 6, the third tubing connection from end G to end H is as follows: 0.22μm air filter - 20cm 1 / 4×7 / 16 inch thermoplastic tubing - 1 / 4×7 / 16 inch double connector - 20cm 1 / 4×7 / 16 inch silicone tubing - 7 / 16 inch Robert clamp - "+" type four connector - two 20cm 1 / 4×7 / 16 inch silicone tubing (+ 7 / 16 inch Robert clamp - 20cm 1 / 4×7 / 16 inch thermoplastic tubing - 0.22μm air filter) - 40cm 1 / 4×7 / 16 inch silicone tubing - 7 / 16 inch Robert clamp - 1 / 4×7 / 16 inch double connector - 30cm 1 / 4×7 / 16 inch thermoplastic tubing - 0.22μm air filter.

[0079] like Figure 7 The sampling pipeline 124 includes an eleventh interface 1611, a twelfth interface 1612 and a thirteenth interface 1613. The first interface 1601 is used for sampling, and the twelfth interface 1612 is connected to an air filter 1502 and is used to inject air into the sampling pipeline 124 to drain the liquid in the pipeline.

[0080] Among them, such as Figure 7 The sampling pipeline 124 may include a thirtieth connecting pipe 1430, a thirtieth connector 1330, a thirty-first connecting pipe 1431, a thirty-first connector 1331, a thirty-second connecting pipe 1432, a thirty-third connecting pipe 1433, a thirty-third connector 1333, and a thirty-fourth connecting pipe 1434. An eleventh interface 1611 is located on the thirtieth connecting pipe 1430, a twelfth interface 1612 is located on the thirty-second connecting pipe 1432, and a thirteenth interface 1613 is located on the thirty-fourth connecting pipe 1434.

[0081] Optionally, at least one of the 30th connecting tube 1430, the 31st connecting tube 1431, and the 33rd connecting tube 1433 is a flexible tube (e.g., a 20cm 3 / 16×5 / 16 inch silicone tube). Optionally, at least one of the 30th connecting tube 1430, the 31st connecting tube 1431, and the 33rd connecting tube 1433 is provided with a corresponding tube clamp 1501 (e.g., a 5 / 16 inch Robert clamp). Optionally, at least one of the 32nd connecting tube 1432 and the 34th connecting tube 1434 is a thermoplastic tube (e.g., a 20cm 3 / 16×5 / 16 inch thermoplastic tube). Optionally, at least one end of the 32nd connecting tube 1432 and the 34th connecting tube 1434 is provided with an air filter 1502 (0.22μm air filter), and the end of the 30th connecting tube 1430 is provided with a sampling head (e.g., a Luer sampling head). Optionally, the thirtieth connector 1330 is a tee connector (such as a 3 / 16×5 / 16 inch "Y" type tee connector). Optionally, the thirty-first connector 1331 and the thirty-third connector 1333 are double connectors (such as a 20cm 3 / 16×5 / 16 inch thermoplastic pipe - 3 / 16×5 / 16 inch double connector). Additionally, the thirtieth connector 1330 can be a "Y" type tee connector. This facilitates material conveying.

[0082] like Figure 7 As shown, Figure 6 As shown, the sampling tubing connections from end I to end J are as follows: 0.22μm air filter - 20cm 3 / 16×5 / 16 inch thermoplastic tubing - 3 / 16×5 / 16 inch double connector - 20cm 3 / 16×5 / 16 inch silicone tubing - 5 / 16 inch Robert clamp - 3 / 16×5 / 16 inch "Y" type tee connector - 20cm 3 / 16×5 / 16 inch silicone tubing - 5 / 16 inch Robert clamp (another branch connects to 10cm 3 / 16×5 / 16 inch silicone tubing - Luer sampling head) - 3 / 16×5 / 16 inch double connector - 20cm 3 / 16×5 / 16 inch thermoplastic tubing - 0.22μm air filter.

[0083] like Figure 8 The replenishment assembly 125 includes a replenishment tank 1254, a first connecting pipe 1251, a second connecting pipe 1252, and a third connecting pipe 1253. The first connecting pipe 1251 connects to the upper space inside the replenishment tank 1254 and is used to connect to the outlet of the reactor 121. The second connecting pipe 1252 connects to the lower space of the replenishment tank 1254 and is used to connect to the inlet of the reactor 121. The third connecting pipe 1253 connects to the lower space of the replenishment tank 1254 and is used to connect to the third main pipeline 122.

[0084] like Figure 8The rehydration assembly 125 is a culture medium rehydration bottle with three ports K1-K3 from left to right. The caps of the three ports are connected to the outside via tubing. A 0.22μm air filter at the end of each tubing ensures a sterile environment inside the device after high-temperature and high-pressure sterilization. The tubing at port K1 connects to the outlet of reactor 121, allowing the liquid inside reactor 121 to flow back into this bottle. It consists of a 0.22μm air filter, a 50cm 1 / 4×7 / 16 inch thermoplastic tube, a 1 / 4×7 / 16 inch double connector, and a 20cm 1 / 4×7 / 16 inch silicone tube. Port K2 has two tubing lines. The shorter line is for ventilation, consisting of a 10cm 3 / 16×5 / 16 inch silicone tubing and a 0.22μm air filter. The longer line connects to the inlet of reactor 121 for replenishing the internal circulating medium, consisting of a 0.22μm air filter, a 50cm 1 / 4×7 / 16 inch thermoplastic tubing, a 1 / 4×7 / 16 inch double connector, and a 50cm 1 / 4×7 / 16 inch silicone tubing. Port K3 is used to empty the culture medium from this replenishment bottle and to add fresh culture medium. It consists of a 0.22μm air filter, a 50cm 1 / 4×7 / 16 inch thermoplastic tubing, a 1 / 4×7 / 16 inch double connector, an 80cm 1 / 4×7 / 16 inch silicone tubing, and a 7 / 16 inch Robert clamp.

[0085] As shown in the figure, the exhaust assembly 126 includes an exhaust tank 1266, a fourth connector 1264 and a fifth connector 1265. The fourth connector 1264 connects to the lower space inside the exhaust tank 1266 and to the outlet of the reactor 121. The fifth connector 1265 connects to the upper space of the exhaust tank 1266 and is used for exhaust.

[0086] like Figure 9 The exhaust assembly is an exhaust bottle, consisting of two pipes and a 250ml blue-capped glass bottle. The glass bottle contains a suitable amount of liquid. The M-end pipe consists of a 10cm 3 / 16×5 / 16 inch silicone tube and a 0.22μm air filter. Gas from reactor 121 enters the bottle through the L-end, passes through the liquid inside, and is exhausted through the M-end pipe. The L-end pipe consists of a 0.22μm air filter, a 20cm 1 / 4×7 / 16 inch thermoplastic tube, a 1 / 4×7 / 16 inch double connector, a 40cm 1 / 4×7 / 16 inch silicone tube, and a 7 / 16 inch Robert clamp.

[0087] The third main pipeline 122 is connected as a single unit. After assembly, the third main pipeline 122 can be sterilized and sealed, improving assembly efficiency and facilitating sterilization. Optionally, the third pipeline 123 is connected as a single unit; optionally, the sampling pipeline 124 is connected as a single unit.

[0088] like Figures 4 to 9 In the cell culture system of this invention, the small-scale test of the disposable fixed-bed bioreactor 121 is conducted in a biosafety cabinet. The third main pipeline 122, the third pipeline 123, the sampling pipeline 124, the replenishment assembly 125, and the exhaust assembly 126 are sterilized in a high-temperature, high-pressure steam sterilizer. Figure 9 The sampling port of reactor 121 is connected to the third main pipeline 122. Two 20cm 1 / 4×7 / 16 inch thermoplastic tubes on the right side of the third main pipeline 122 are aseptically connected to sampling pipeline 124 and replenishment assembly 125 respectively via an aseptic connector. The 30cm 1 / 4×7 / 16 inch thermoplastic tube at the lower end of the third main pipeline 122 is aseptically connected to the third pipeline 123. The exhaust assembly 126 is connected to the gas outlet pipeline on reactor 121. Port K1 on replenishment assembly 125 is connected to the outlet on reactor 121, and port K2 is connected to the inlet on reactor 121. This reactor 121 piping connection device allows for convenient circulation replenishment of reactor 121, discharge of waste culture medium, and facilitates process sampling and testing.

[0089] This invention provides a tubing connection device for culturing 293 cells using a cell factory and bioreactor 121 process in upstream cell culture. This cell culture tubing connection device is easy to mass-produce, streamlining the cell culture process, reducing operational differences between personnel, and minimizing batch-to-batch errors. Using this tubing connection in the cell factory and bioreactor 121 process can improve production efficiency, shorten operation time, and, more importantly, reduce the risk of contamination, providing a reliable guarantee for culturing 293 cells in the cell factory and bioreactor 121.

[0090] The cell culture system of this invention may include: 25# silicone tubing (i.e., 1 / 4×7 / 16 inch silicone tubing), 24# silicone tubing (i.e., 3 / 16×5 / 16 inch silicone tubing), 1 / 4×7 / 16 inch thermoplastic tubing, 1 / 4 inch double connector, 1 / 4 inch cross connector, 1 / 4 inch tee Y connector, air filter 1502, cable ties, 7 / 16 Robert clips, 250ml blue cap glass bottle, 5000ml blue cap glass bottle, and sterile breathing bag.

[0091] In the description of this utility model, it should be understood that the terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc., indicating the orientation or positional relationship are based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this utility model and simplifying the description, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this utility model.

[0092] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this utility model, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0093] In this utility model, unless otherwise explicitly specified and limited, the terms "installation," "connection," "joining," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components, unless otherwise explicitly limited. Those skilled in the art can understand the specific meaning of the above terms in this utility model according to the specific circumstances.

[0094] In this utility model, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature is in indirect contact with the second feature through an intermediate medium. Furthermore, "above," "on top of," and "over" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0095] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0096] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A cell culture system, characterized in that, include: A material conveying device, comprising at least two material conveying ports and a material output port, wherein the at least two material conveying ports are used to input at least two kinds of materials, and the material output port is used to output materials; A material distribution unit, comprising a material input port and at least one material distribution port, wherein the material input port is connected to the material output port and is used to receive materials output by the material conveyor, and the material distribution port is used to connect to a cell factory to provide materials to the cell factory.

2. The cell culture system according to claim 1, characterized in that, The material conveying component includes a first main pipeline and at least two secondary pipelines. The material conveying port is located at one end of the primary pipeline, and the other end of the primary pipeline is connected to the first main pipeline. The material output port is located at the first main pipeline.

3. The cell culture system according to claim 2, characterized in that, The first main pipeline includes a first connector, a first connecting pipe, a second connector, a second connecting pipe, a third connector, and a third connecting pipe connected in sequence, and the material outlet is located at the end of the third connecting pipe; The at least two primary pipelines connect the first connector and / or the second connector. The primary pipeline includes a fourth connecting pipe, a fourth connector, and a fifth connecting pipe connected in sequence. The material conveying port is located at the end of the fourth connecting pipe, and the end of the fifth connecting pipe is connected to the first main pipeline.

4. The cell culture system according to claim 3, characterized in that, At least one of the first connecting pipe, the second connecting pipe, and the fifth connecting pipe is a flexible hose; and / or, at least one of the first connecting pipe, the second connecting pipe, and the fifth connecting pipe is provided with a corresponding pipe clamp; and / or, at least one of the third connecting pipe and the fourth connecting pipe is a thermoplastic pipe; and / or, at least one of the third connecting pipe and the fourth connecting pipe is provided with an air filter at its end; and / or, the first connector is a tee connector; and / or, the second connector is a four-way connector; and / or, the third connector and the fourth connector are two-way connectors.

5. The cell culture system according to claim 1, characterized in that, The material distribution component includes a second main pipeline and at least one secondary pipeline. The material distribution port is located at one end of the secondary pipeline, and the other end of the secondary pipeline is connected to the second main pipeline. The material input port is located on the second main pipeline.

6. The cell culture system according to claim 5, characterized in that, The second main pipeline includes a sixth connecting pipe, a sixth connector, a seventh connecting pipe, and a seventh connector connected in sequence, with the material inlet located at the end of the sixth connecting pipe; The second pipeline includes an eighth connecting pipe, an eighth connector, and a ninth connecting pipe connected in sequence. The eighth connecting pipe is connected to the seventh connector, and the material distribution port is located at the end of the ninth connecting pipe.

7. The cell culture system according to claim 6, characterized in that, At least one of the seventh and eighth connecting pipes is a flexible hose; and / or, at least one of the seventh and eighth connecting pipes is provided with a corresponding pipe clamp; and / or, at least one of the sixth and ninth connecting pipes is a thermoplastic pipe; and / or, at least one of the sixth and ninth connecting pipes is provided with an air filter at its end; and / or, the seventh connector is a four-way connector; and / or, the sixth and eighth connectors are two-way connectors.

8. The cell culture system according to claim 1, characterized in that, The material conveying components are connected as a single unit. And / or, the material distribution components are connected as a single unit; And / or, the cell culture system further includes a drive unit, which is connected to the material conveyor and the material dispenser, and communicates with the material output port and the material input port. The drive unit is used to drive the material to flow from the material output port to the material input port. And / or, the material distribution port includes a plurality of ports, which are connected to the material input port, and each material distribution port is adapted to connect to a cell factory; And / or, the at least two material transfer ports are respectively used to connect the culture medium, DPBS, trypsin, and waste bag.

9. A cell culture system, characterized in that, The cell culture system further includes a reactor, a third main pipeline, a third secondary pipeline, a sampling pipeline, a replenishment component, and an exhaust component. The third main pipeline connects the sampling port of the reactor, the third secondary pipeline, the sampling pipeline, and the replenishment component. The replenishment component connects the liquid outlet of the reactor, the liquid inlet of the reactor, and the third main pipeline. The exhaust component connects the gas outlet of the reactor.

10. The cell culture system according to claim 9, characterized in that, The third main pipeline also includes a first interface and a second interface. The first interface is configured to connect to the virus solution during the inoculation process, and the second interface is configured to connect to the cell inoculation tank. And / or, the third pipeline further includes a seventh interface, an eighth interface and a ninth interface, wherein the seventh interface is configured to be connected to a waste liquid bag, the eighth interface is configured to be connected to a culture medium storage bag, and the ninth interface is configured to drain the pipeline liquid; And / or, the sampling pipeline further includes an eleventh interface and a twelfth interface, the eleventh interface being used for sampling, and the twelfth interface being connected to an air filter and used to inject air into the sampling pipeline to drain the liquid in the pipeline. And / or, the replenishment assembly includes a replenishment tank, a first connecting pipe, a second connecting pipe, and a third connecting pipe, wherein the first connecting pipe communicates with the upper space inside the replenishment tank and is used to connect to the outlet of the reactor, the second connecting pipe communicates with the lower space of the replenishment tank and is used to connect to the inlet of the reactor, and the third connecting pipe communicates with the lower space of the replenishment tank and is used to connect to the third main pipeline. And / or, the exhaust assembly includes an exhaust canister, a fourth connector and a fifth connector, the fourth connector communicating with the lower space inside the exhaust canister and communicating with the exhaust outlet of the reactor, and the fifth connector communicating with the upper space of the exhaust canister and being used for exhaust; And / or, the third main pipeline is connected as a single unit; And / or, the third pipeline connection is an integral structure; And / or, the sampling pipeline is connected as an integral structure.

Images