Cell factory reactor and use method thereof

Abstract

The embodiment of the invention provides a cell factory reactor and a use method, and relates to the technical field of cell culture, the cell factory reactor comprises: a cell factory main body having a plurality of culture layers and a first channel respectively communicated with the plurality of culture layers, each culture layer having an upper surface and a lower surface, both the upper surface and the lower surface being subjected to TC treatment; the sensing assembly is used for acquiring culture environment parameters in the cell factory main body; the process gas supply assembly is connected with the first channel; the pipeline system comprises a liquid input assembly and a liquid output assembly, the liquid input assembly is used for conveying materials required by cell culture to the first channel, and the liquid output assembly is used for transferring liquid or cell suspension in the cell factory main body to the outside of the cell factory main body; the controller comprises a swinging mechanism, and the swinging mechanism is used for driving the cell factory main body to swing. According to the embodiment of the invention, the scale of cell amplification is increased, and the problem of insufficient amplification scale of a traditional cell factory is effectively solved.

Description

Technical Field

[0001] This application relates to the field of cell culture technology, and in particular to a cell factory reactor and its usage method. Background Technology

[0002] In related technologies, the large-scale expansion of adherent cells has a wide range of applications; however, scaling up the expansion scale has always been a technical challenge. Existing solutions include 2D and 3D culture modes. 3D culture is complex to operate, costly, and alters cell growth characteristics, which is detrimental to scientific research and applications. A common traditional 2D culture method is cell factory culture. Common cell factory culture essentially involves stacking multiple layers of culture flasks, which linearly increases the surface area, thereby expanding the scale of cell culture. A typical 10-layer cell factory has a surface area of ​​approximately 6320 cm². 2 The harvestable cell quantity is at the 6E8 level, the expansion quantity is limited, and due to the large number of layers and insufficient dissolved oxygen, uneven cell growth is likely to occur, affecting cell quality. Summary of the Invention

[0003] This application aims to address at least one of the technical problems existing in the prior art. To this end, this application proposes a cell factory reactor and method that can effectively increase the scale of cell culture while improving the quality of cell culture.

[0004] An embodiment of the first aspect of this application provides a cell factory reactor, comprising:

[0005] The cell factory body has multiple culture layers and a first channel communicating with each of the multiple culture layers, wherein each culture layer has an upper surface and a lower surface, and both the upper surface and the lower surface are treated with TC.

[0006] A sensing component is used to acquire culture environment parameters within the cell factory body, including pH value, temperature, and dissolved oxygen level.

[0007] A process gas supply component is connected to the first channel, and the process gas supply component is used to supply process gases to the cell factory body according to the culture environment parameters;

[0008] The piping system includes a liquid inlet assembly and a liquid outlet assembly. The liquid inlet assembly is used to deliver substances required for cell culture into the first channel, and the liquid outlet assembly is used to transfer liquid or cell suspension within the cell factory body to the outside of the cell factory body.

[0009] The controller includes a swing mechanism for driving the cell factory body to swing.

[0010] Furthermore, the liquid input assembly includes a first bottom tube, a first conduit, and a first peristaltic pump. One end of the first bottom tube extends into the middle of the first channel, and the other end of the first bottom tube is connected to one end of the first conduit. The other end of the first conduit has multiple liquid inlet ends, each of which is used to connect to a different transfer bag. The first peristaltic pump is used to drive the cells or materials stored in each of the transfer bags to transfer into the cell factory body.

[0011] Furthermore, the liquid output assembly includes a second bottom tube, a second pipeline, and a second peristaltic pump. One end of the second bottom tube extends to the bottom of the first channel, and the other end of the second pipeline is used to connect to a cell harvest bag or a waste liquid bag. The second peristaltic pump is used to drive the waste liquid in the cell factory body to transfer from the second pipeline to the waste liquid bag, or to transfer the cell suspension in the cell factory body to the cell harvest bag.

[0012] Furthermore, the swing mechanism includes a first driving member, a first movable bracket, a second driving member, and a second movable bracket;

[0013] The first driving component is used to drive the first movable bracket to rotate around the first axis;

[0014] The second movable bracket is mounted on the first movable bracket, and the second driving member is used to drive the second movable bracket to rotate around the second axis;

[0015] The second movable support is used to connect to the main body of the cell factory, and the first axis is perpendicular to the second axis.

[0016] Furthermore, the rotation angle range of the first movable support is -90° to 90°; and / or, the rotation angle range of the second movable support is -90° to 90°.

[0017] Furthermore, the swing mechanism has a liquid inlet position. When the swing mechanism is in the liquid inlet position, the angle between the first movable support and the initial position is 20°, and the angle between the second movable support and the initial position is 20°.

[0018] Furthermore, the swing mechanism has a liquid outlet position. When the swing mechanism is in the liquid outlet position, the angle between the first movable support and the initial position is 20°, and the angle between the second movable support and the initial position is 20°.

[0019] Furthermore, it also includes an air filter installed on the main body of the cell factory, the air filter being used to balance the gas pressure inside and outside the main body of the cell factory.

[0020] Furthermore, the controller includes a heating system for heating the cell factory body based on the temperature obtained by the sensing component, so as to adjust the internal temperature of the cell factory body in real time.

[0021] An embodiment of the second aspect of this application provides a method for applying a cell factory reactor, which is used in the cell factory reactor as described above, and includes the following steps:

[0022] The cell factory body is mounted on the swing mechanism, culture medium is pumped into the cell factory body, and the swing mechanism is used to drive the cell factory body to rotate, thereby controlling the temperature inside the cell factory body to be adjusted to a preset temperature.

[0023] The cell culture materials and cell seeds are pumped into the main body of the cell factory, the swing mechanism is controlled to rotate in the first rotation mode, and the temperature, dissolved oxygen and pH value inside the cell factory are controlled in real time.

[0024] When it is time to harvest cells, the swing mechanism is used to control the rotation of the cell factory body so that one end of the liquid output component inside the cell factory body is located at the lowest point of the cell factory body, and the cells inside the cell factory body are transferred to the cell collection bag through the liquid output component.

[0025] As can be seen from the above technical solutions, the embodiments of this application have at least the following beneficial effects:

[0026] In the cell factory reactor and method provided in this application, the upper and lower surfaces of the culture layers are treated with TC (temperature-controlled oxidation), and a swinging mechanism drives the cell factory body to rotate and oscillate. This allows the culture medium within the cell factory body to flow over the upper and lower surfaces of each culture layer, thereby increasing the culture area and significantly expanding the scale of cell expansion, effectively solving the problem of insufficient expansion scale in traditional cell factories. Simultaneously, in the embodiments of this application, the cell factory reactor can monitor the dissolved oxygen and temperature of the culture medium within the cell factory body in real time through sensing components. This facilitates real-time perfusion and medium exchange based on the culture environment parameters within the cell factory reactor, regulating the cell growth environment and improving cell culture quality. Furthermore, the cell factory reactor of this application can independently control cell growth conditions and provide real-time feedback, eliminating the need for a separate incubator and reducing cell culture costs. Attached Figure Description

[0027] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0028] Figure 1 This is a three-dimensional structural schematic diagram of a cell factory reactor provided in one embodiment of this application;

[0029] Figure 2 This is a front view schematic diagram of a cell factory reactor provided in one embodiment of this application;

[0030] Figure 3 This is a top view of a cell factory reactor provided in one embodiment of this application;

[0031] Figure 4 for Figure 3 A schematic diagram of the cross-sectional structure at position AA in the middle;

[0032] Figure 5 This is a schematic diagram of the main structure of the cell factory in one embodiment of this application;

[0033] Figure 6 This is a cross-sectional view of one location of the cell factory body in one embodiment of this application.

[0034] Figure label:

[0035] 100. Main body of the cell factory; 110. First interface; 120. Second interface; 130. Culture layer; 131. Upper surface; 132. Lower surface; 140. First channel;

[0036] 200, swing mechanism; 210, fixed bracket; 220, first driving component; 230, first movable bracket; 240, second driving component; 250, second movable bracket; 260, fastening assembly; 270, position sensor. Detailed Implementation

[0037] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0038] See Figure 1As shown, an embodiment of the first aspect of this application discloses a cell factory reactor, including a cell factory body 100, a sensing component, a process gas supply component, a piping system, and a controller.

[0039] Specifically, the cell factory body 100 has multiple culture layers 130 and a first channel 140, which is connected to the multiple culture layers 130. Each culture layer 130 has an upper surface 131 and a lower surface 132. Both the upper surface 131 and the lower surface 132 are treated with TC so that the upper surface 131 and the lower surface 132 of each culture layer 130 can be used for cell adhesion culture, which helps to increase the culture surface area and thus increase the scale of cell expansion.

[0040] The sensing component is used to acquire the culture environment parameters within the cell factory body 100, including pH, temperature, and dissolved oxygen levels, and feeds them back to the controller in real time. Thus, in practical applications, the culture environment within the cell factory body 100 can be adjusted in real time based on parameters such as pH, temperature, and dissolved oxygen levels to regulate cell growth and optimize cell culture quality.

[0041] The process gas supply component is connected to the first channel 140 and is used to supply process gases to the cell factory main body 100 according to the culture environment parameters. The process gases can be carbon dioxide, oxygen, or other process gases. In practical applications, process gases can be replenished to the cell factory main body 100 in real time based on parameters such as pH value and dissolved oxygen level obtained by the sensing component.

[0042] The piping system includes a liquid inlet component and a liquid outlet component. The liquid inlet component is used to deliver substances required for cell culture into the first channel 140, and the liquid outlet component is used to transfer culture medium or cell suspension from inside the cell factory main body 100 to the outside of the cell factory main body 100. Specifically, substances required for cell culture include buffer solutions, trypsin, culture medium, pH adjustment solutions, etc. The liquid inlet component is used to introduce cells, buffer solutions, trypsin, culture medium, pH adjustment solutions, etc., related to the culture process into the cell factory main body 100.

[0043] The controller includes a swing mechanism 200, which drives the cell factory body 100 to swing so that the cell factory body 100 can swing, allowing the culture medium to flow over the upper surface 131 and lower surface 132 of the culture layer 130, thereby enabling cell adhesion culture to be performed on both the upper surface 131 and lower surface 132 of the culture layer 130.

[0044] In the cell factory reactor provided in this application embodiment, by treating the upper surface 131 and lower surface 132 of the culture layer 130 with TC, and coordinating with the swing mechanism 200 to drive the cell factory body 100 to rotate and swing, the culture medium within the cell factory body can flow over the upper surface 131 and lower surface 132 of each culture layer 130, thereby increasing the culture area and greatly increasing the scale of cell expansion, effectively solving the problem of insufficient expansion scale in traditional cell factories. Simultaneously, in this application embodiment, the cell factory reactor can monitor the dissolved oxygen and temperature of the culture medium within the cell factory body 100 in real time, facilitating real-time perfusion and medium exchange based on the culture environment parameters within the cell factory reactor, regulating the cell growth environment, and improving cell culture quality. Furthermore, the cell factory reactor of this application can independently control cell growth conditions and provide real-time feedback, eliminating the need for a separate incubator and reducing cell culture costs.

[0045] In this embodiment, the sensing components include a pH sensor, a dissolved oxygen sensor, and a temperature sensor, which are used to monitor the pH value, temperature, and dissolved oxygen in the culture medium inside the cell factory body 100 online, and provide feedback to the controller and record in real time. This allows the controller to control the liquid input and liquid output components to perform perfusion or medium replacement operations based on parameters such as pH value, temperature, and dissolved oxygen in the culture medium inside the cell culture body 100.

[0046] In one embodiment, the liquid input assembly includes a first bottom tube, a first conduit, and a first peristaltic pump. One end of the first bottom tube extends into the middle of a first channel 140, and the other end of the first bottom tube is connected to one end of the first conduit. The other end of the first conduit has multiple inlet terminals, each for connecting to a different transfer bag. The first peristaltic pump drives the cells or materials stored in each transfer bag to the cell factory main body 100. The contents of each transfer bag can be configured as needed. For example, each transfer bag can contain process-related cells, buffer solutions, trypsin, culture media, pH adjustment solutions, etc. The first peristaltic pump pumps the required substances simultaneously or separately into the cell factory main body 100 as needed. It is understood that the number and specifications of the inlet terminals of the first conduit can be adjusted according to process requirements.

[0047] In one embodiment, the controller includes a control system for controlling the swing mechanism 200 to swing, and also for controlling the liquid input component to pump in the substances required for culture and controlling the liquid output component to pump out cell suspension or waste liquid, etc.

[0048] In this embodiment, the control system is used to control the operation of the first peristaltic pump according to the culture environment parameters obtained by the sensing component, thereby controlling the liquid input component to input the substances required for cell culture into the cell factory body 100.

[0049] In one embodiment, the liquid output assembly includes a second bottom tube, a second conduit, and a second peristaltic pump. One end of the second bottom tube extends to the bottom of the first channel 140, and the other end of the second conduit is used to connect to a cell harvest bag or a waste liquid bag. The second peristaltic pump is used to drive waste liquid in the cell factory body 100 from the second conduit to the waste liquid bag, or to transfer cell suspension in the cell factory body 100 to the cell harvest bag. The second bottom tube extends to the bottom of the first channel 140, that is, to the bottom of the cell factory body 100. Thus, the second peristaltic pump can transfer part or all of the liquid in the cell factory body 100 out, or harvest the cell suspension into the cell harvest bag.

[0050] In this embodiment, the control system is used to control the operation of the second peristaltic pump, thereby controlling the liquid output component to transfer the liquid or cell suspension inside the cell factory body 100 to the outside of the cell factory body 100.

[0051] In one embodiment, see Figures 1 to 4 The swing mechanism 200 includes a first drive member 220, a first movable support 230, a second drive member 240, and a second movable support 250. The first drive member 220 drives the first movable support 230 to rotate around a first axis. The second movable support 250 is mounted on the first movable support 230, and the second drive member 240 drives the second movable support 250 to rotate around a second axis. The second movable support 250 is connected to the cell factory body 100, and the first axis is perpendicular to the second axis. In the figure, the first axis is represented by X, and the second axis is represented by Y. By rotating the first movable support 230 around the first axis X and the second movable support 250 around the second axis Y, the culture medium and other culture materials can flow to various positions of each culture layer 130, thus enabling cell adhesion culture at each position of the culture layer 130. In this embodiment, both the first drive member 220 and the second drive member 240 are motors.

[0052] Meanwhile, in the above embodiments, by controlling the coordinated rotation of the first movable support 230 and the second movable support 250, the substances required for cell culture input by the liquid input component can be distributed to each culture layer 130 during liquid input, and each culture layer 130 can be tilted during cell harvesting so that the second bottom tube of the liquid output component is at its lowest position, thereby facilitating the partial or complete transfer of liquid or cell suspension in the cell factory body 100 to the outside of the cell factory.

[0053] In this embodiment, please refer to Figures 1 to 3 The controller includes a fixed bracket 210, and a first movable bracket 230 is rotatably connected to the fixed bracket 210 via a rotating shaft and bearings, so that the first movable bracket 230 can rotate relative to the fixed bracket 210.

[0054] Further, see Figures 1 to 4 The controller includes a fastening assembly 260, which is mounted on a second movable support 250. The second movable support 250 has a receiving cavity for accommodating the cell factory body 100. Once the cell factory body 100 is placed in the receiving cavity, the fastening assembly 260 can clamp the cell factory body 100.

[0055] In one possible implementation, the fastening assembly 260 includes a fastening bolt, and the second movable bracket 250 is provided with a threaded through hole. The fastening bolt is threadedly connected to the threaded through hole and abuts against the cell factory body 100 at one end to fix the cell factory body 100 to the second movable bracket 250.

[0056] In one embodiment, see Figures 1 to 3 The rotation angle range of the first movable support 230 is -90° to 90°.

[0057] Furthermore, the rotation angle range of the second movable support 250 is -90° to 90°.

[0058] Thus, during the culture material input stage, the liquid input component can input the materials required for cell adhesion culture into the first channel 140, and these materials can flow from the first channel 140 to other locations in each culture layer 130; during the waste liquid transfer or cell harvesting stage, the liquid or cell suspension in each culture layer 130 can be gathered at the first channel 140, thereby facilitating the transfer of waste liquid or cell suspension to the outside of the cell factory body 100.

[0059] It is worth understanding that, in the above embodiments, see Figure 1 With the first movable support 230 in its initial position (horizontal position) and its angle set to 0°, and ω1 as the positive direction of rotation of the first movable support 230, for example, when the first movable support 230 rotates 30° from its initial position along the ω1 direction, the rotation angle of the first movable support 230 is positive 30°. Similarly, with the second movable support 250 in its initial position (horizontal position) and its angle set to 0°, and ω2 as the positive direction of rotation of the second movable support 250, for example, when the second movable support 250 rotates 30° from its initial position along the ω2 direction, the rotation angle of the first movable support 230 is positive 30°.

[0060] In this embodiment, see Figure 1 Position sensors 270 are respectively provided on the first movable support 230 and the second movable support 250. One position sensor 270 is used to detect the relative position of the first movable support 230 with respect to the initial position, and the other position sensor 270 is used to detect the relative position of the second movable support 270 with respect to the initial position.

[0061] Furthermore, in one embodiment, the oscillating mechanism 200 has a liquid inlet position. When the oscillating mechanism 200 is in the liquid inlet position, the angle between the first movable support 230 and the initial position is 20°, and the angle between the second movable support 250 and the initial position is also 20°. This allows the cell culture material input by the liquid input component to flow conveniently to various positions of each culture layer 130.

[0062] In one embodiment, the oscillating mechanism 200 has a liquid outlet position. When the oscillating mechanism 200 is in the liquid outlet position, the angle between the first movable support 230 and the initial position is 90°, and the angle between the second movable support 250 and the initial position is 45°. This allows for convenient collection of liquid or cell suspension within the cell factory body 100, facilitating the transfer of liquid or cell suspension from the cell factory body 100.

[0063] It is understandable that when the swing mechanism 200 is in the liquid outlet position, the bottom of the first channel 140 is located at the lowest point of the cell factory body 100.

[0064] In this embodiment, the upper end of the first channel 140 is connected to the first interface 110 of the cell factory body 100, and the other end extends downward along the thickness direction of the culture layer 130. The liquid input component delivers the substances required for cell culture into the cell factory body 100 through the first interface 110.

[0065] In one embodiment, the cell factory reactor includes an air filter installed in the cell factory body 100, the air filter being used to balance the gas pressure inside and outside the cell factory body 100.

[0066] In this embodiment, see Figure 1 An air filter is installed on the second interface 120. The cell factory body 100 has a second channel that connects to each culture layer 130. One end of the second interface 120 is connected to the second channel. In practical applications, the air filter can be used to balance the gas pressure inside and outside the cell factory. When the air filter is removed, the second interface 120 can be used as a manual liquid inlet and / or outlet interface.

[0067] In one embodiment, the controller includes a heating system for heating the cell factory body 100 based on the temperature obtained by the sensing components, so as to regulate the internal temperature of the cell factory body 100 in real time.

[0068] As can be seen from the foregoing description, the cell factory reactor in the embodiments of this application has the following advantages:

[0069] 1. The cell culture surface area of ​​the cell factory reactor disclosed in the embodiments of this application is larger than that of traditional cell factory culture, which greatly increases the scale of cell expansion and effectively solves the problem of insufficient expansion scale of traditional cell factories.

[0070] 2. Traditional cell factories rely on manual operation, which is difficult due to their large size. The cell factory reactor disclosed in this application uses an automated swing mechanism 200 and a control system to automatically complete the process operations, making it very convenient.

[0071] 3. Traditional cell factories are large in size and require large incubators for cultivation. The cell factory reactor disclosed in the embodiments of this application can independently control cell growth conditions and provide real-time feedback, eliminating the need for a separate incubator.

[0072] 4. Traditional cell factories lack monitoring methods for cell growth, cannot monitor dissolved oxygen and temperature in the culture medium, and cannot change the medium in real time. The cell factory reactor in this embodiment can monitor dissolved oxygen and temperature in the culture medium in real time, and can change the medium in real time according to the parameters in the reactor, thereby regulating the cell growth environment and optimizing cell quality.

[0073] 5. Traditional cell factory operations are cumbersome and require completion within a biosafety cabinet under a Class B environment. This results in high construction costs and significant reliance on manual labor, posing a considerable risk of contamination. The cell factory reactor in this embodiment employs a fully enclosed pipeline system with aseptic welding connections, greatly reducing the risk of contamination. Furthermore, culture operations can be completed in a Class C environment, eliminating the need for a Class B sterile environment and significantly reducing construction and maintenance costs.

[0074] An embodiment of the second aspect of this application discloses a method for applying a cell factory reactor, which is applied to the cell factory reactor as described above, and includes the following steps:

[0075] The cell factory body 100 is mounted on the swing mechanism 200, culture medium is pumped into the cell factory body 100, and the swing mechanism 200 is used to drive the cell factory body 100 to rotate, thereby controlling the temperature inside the cell factory body 100 to be adjusted to the preset temperature.

[0076] Cell culture material and cell seeds are pumped into the cell factory body 100, the swing mechanism 200 is controlled to rotate in the first rotation mode, and the temperature, dissolved oxygen and pH value in the cell factory are controlled in real time to start cell culture.

[0077] The controller perfuses the main body of the cell factory according to process requirements;

[0078] When it is time to harvest cells, the cell factory body 100 is rotated by the swing mechanism 200 so that one end of the liquid output component inside the cell factory body 100 is located at the lowest point of the cell factory body 100, and the cells inside the cell factory body 100 are transferred to the cell collection bag through the liquid output component.

[0079] In one embodiment, the cell factory reactor is used as follows: (In actual applications, adjustments can be made according to process requirements).

[0080] 1) Inside the biosafety cabinet, unpack the cell factory reactor and check that all components of the cell factory reactor are tightly connected and in good condition. Clamp the tubes of each component.

[0081] 2) Remove the cell factory reactor from the biosafety cabinet and install it into the swing mechanism 200 of the controller. Connect the culture medium using a sterile connector and install the culture medium tubing into the corresponding peristaltic pump. Pump in an appropriate amount of culture medium, turn on the automatic rotation mode, and balance the temperature inside the cell factory reactor until the internal temperature reaches the preset temperature.

[0082] 3) Connect the liquid input component of the cell factory reactor to the required bag and seed cell bag, pump in the cell seeds for inoculation, turn on the low-speed rotation mode and control the temperature, dissolved oxygen, pH, etc., and start the culture.

[0083] 4) The controller perfuses the cell factory reactor according to process requirements.

[0084] 5) When the cell factory reactor needs to harvest cells, connect the trypsin and buffer bags to the reactor and install them into the corresponding peristaltic pump. Tilt the cell factory body 100 so that the second bottom tube is at the lowest point of the cell factory body 100. Repeat this tilting operation whenever liquid needs to be drained. Drain the culture medium from the cell factory body 100, pump in an appropriate amount of buffer, shake to mix, and then tilt to drain the liquid from the cell factory body 100. Pump in an appropriate amount of trypsin, and then set the reactor to mixing mode to allow the trypsin to wet the entire inner surface of the cell factory body 100. Then tilt to drain any excess trypsin from the cell factory body 100. Maintain the temperature at 37°C and rotate slowly. After the appropriate digestion time, pump in an appropriate amount of culture medium to stop digestion. At this point, set the reactor to strong shaking mode to elute the cells. Tilt the cell factory body 100 to collect the cells into the cell collection bag, and heat-seal the cell collection bag to obtain the harvested cells.

[0085] The cell factory reactor and its usage method of this application are described in detail below with a specific embodiment.

[0086] In this embodiment, a cell factory reactor is used to culture MSC cells as an example. It is worth understanding that the cell factory reactor of this application can also be used to culture other cells, and is not limited thereto.

[0087] 1) Preparing the cell factory reactor: Install the cell factory reactor into the swing mechanism 200 of the controller, and connect the required reagent bags, such as culture medium, PBS buffer, and trypsin, to the inlet end of the cell factory reactor (i.e., the inlet end of the liquid input component) using a sterile connector. Connect the waste bag and cell harvest bag to the outlet end of the cell factory reactor (i.e., the outlet end of the liquid output component).

[0088] 2) Preparing seed cells: Resuspend 1E8 MSC cells in 1L of culture medium, mix well, and fill into a storage bag to serve as the seed cell bag. Aseptically connect the seed cell bag to the inlet end of the cell factory reactor.

[0089] 3) Subsequent inoculation, cultivation, and harvesting shall be carried out as follows:

[0090]

[0091] In the table above, X20° indicates that the angle between the first movable support 230 and its initial position is +20°, and the value is the same; similarly, Y20° indicates that the angle between the second movable support 250 and its initial position is +20°.

[0092] In the description of this application, it should be understood that the terms "center", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application.

[0093] 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 technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this application, unless otherwise stated, "a plurality of" means two or more.

[0094] In the description of this application, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection between two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0095] In the description of this specification, specific features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or examples.

[0096] It should be understood that although the steps in the flowcharts of the accompanying figures are shown sequentially as indicated by the arrows, these steps are not necessarily executed in the order indicated by the arrows. Unless explicitly stated herein, there is no strict order restriction on the execution of these steps, and they can be executed in other orders. Moreover, at least some steps in the flowcharts of the accompanying figures may include multiple sub-steps or multiple stages. These sub-steps or stages are not necessarily completed at the same time, but can be executed at different times, and their execution order is not necessarily sequential, but can be performed alternately or in turn with other steps or at least some of the sub-steps or stages of other steps.

Claims

1. A cell factory reactor, characterized in that, include: The cell factory body has multiple culture layers and a first channel communicating with each of the multiple culture layers, wherein each culture layer has an upper surface and a lower surface, and both the upper surface and the lower surface are treated with TC. A sensing component is used to acquire culture environment parameters within the cell factory body, including pH value, temperature, and dissolved oxygen level. A process gas supply component is connected to the first channel, and the process gas supply component is used to supply process gases to the cell factory body according to the culture environment parameters; The piping system includes a liquid inlet assembly and a liquid outlet assembly. The liquid inlet assembly is used to deliver substances required for cell culture into the first channel, and the liquid outlet assembly is used to transfer liquid or cell suspension within the cell factory body to the outside of the cell factory body. The controller includes a swing mechanism for driving the cell factory body to swing.

2. The cell factory reactor according to claim 1, characterized in that, The liquid input assembly includes a first bottom tube, a first conduit, and a first peristaltic pump. One end of the first bottom tube extends into the middle of the first channel, and the other end of the first bottom tube is connected to one end of the first conduit. The other end of the first conduit has multiple liquid inlet ends, each of which is used to connect to a different transfer bag. The first peristaltic pump is used to drive the cells or materials stored in each of the transfer bags to be transferred into the cell factory body.

3. The cell factory reactor according to claim 1, characterized in that, The liquid output assembly includes a second bottom tube, a second pipeline, and a second peristaltic pump. One end of the second bottom tube extends to the bottom of the first channel, and the other end of the second pipeline is used to connect to a cell harvest bag or a waste liquid bag. The second peristaltic pump is used to drive the waste liquid in the cell factory body to transfer from the second pipeline to the waste liquid bag, or to transfer the cell suspension in the cell factory body to the cell harvest bag.

4. The cell factory reactor according to any one of claims 1 to 3, characterized in that, The swing mechanism includes a first driving component, a first movable bracket, a second driving component, and a second movable bracket; The first driving component is used to drive the first movable bracket to rotate around the first axis; The second movable bracket is mounted on the first movable bracket, and the second driving member is used to drive the second movable bracket to rotate around the second axis; The second movable support is used to connect to the main body of the cell factory, and the first axis is perpendicular to the second axis.

5. The cell factory reactor according to claim 4, characterized in that, The rotation angle range of the first movable support is -90° to 90°; and / or, the rotation angle range of the second movable support is -90° to 90°.

6. The cell factory reactor according to claim 5, characterized in that, The swing mechanism has a liquid inlet position. When the swing mechanism is in the liquid inlet position, the angle between the first movable support and the initial position is 20°, and the angle between the second movable support and the initial position is 20°.

7. The cell factory reactor according to claim 5, characterized in that, The swing mechanism has a liquid outlet position. When the swing mechanism is in the liquid outlet position, the angle between the first movable support and the initial position is 20°, and the angle between the second movable support and the initial position is also 20°.

8. The cell factory reactor according to claim 1, characterized in that, It also includes an air filter, which is installed in the main body of the cell factory and is used to balance the gas pressure inside and outside the main body of the cell factory.

9. The cell factory reactor according to claim 1, characterized in that, The controller includes a heating system for heating the cell factory body based on the temperature obtained by the sensing component, so as to adjust the internal temperature of the cell factory body in real time.

10. A method for applying a cell factory reactor, characterized in that, The application to the cell factory reactor as described in any one of claims 1 to 9 includes the following steps: The cell factory body is mounted on the swing mechanism, culture medium is pumped into the cell factory body, the swing mechanism drives the cell factory body to rotate, and the temperature inside the cell factory body is controlled to be adjusted to a preset temperature. The cell culture materials and cell seeds are pumped into the main body of the cell factory, the swing mechanism is controlled to rotate in the first rotation mode, and the temperature, dissolved oxygen and pH value inside the cell factory are controlled in real time. When it is time to harvest cells, the swing mechanism is used to control the rotation of the cell factory body so that one end of the liquid output component inside the cell factory body is located at the lowest point of the cell factory body, and the cells inside the cell factory body are transferred to the cell collection bag through the liquid output component.

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