Bioreactor module structure and parallel bioreactor system

Abstract

The utility model discloses a kind of biological reaction module structure and parallel biological reaction system.Biological reaction module structure includes connecting substrate and setting on connecting substrate liquid-adding assembly, gas joint and reaction tank integrated structure, the reaction tank integrated structure with the connecting substrate can occur the relative motion of no resistance along the axial direction of the reaction tank integrated structure;The liquid-adding assembly is connected with the reaction tank integrated structure through liquid inlet pipeline, the gas joint is connected with the reaction tank integrated structure through gas conveying pipeline, and the reaction tank integrated structure is at least used to provide controllable environment for biological culture.The utility model can make multiple reaction units in parallel biological reaction system under same experimental condition, to ensure the consistency of experimental condition.

Description

Technical Field

[0001] This utility model specifically relates to a bioreaction module structure and a parallel bioreaction system, belonging to the field of cell and microbial culture technology in the production and research and development of food and pharmaceuticals. Background Technology

[0002] To achieve rapid production of the aforementioned protein drugs, antibodies, vaccines, and fermentation products, a bioreactor—equipment capable of large-scale cell culture—is essential. Bioreactors serve as a bridge between laboratory research and industrial-scale production of vaccines and protein drugs. High-throughput screening is a crucial technique in life sciences and drug innovation, its core being the acquisition of a large amount of information from a single experiment, identifying valuable insights, and shortening the research and development cycle. The screening and validation of stable, highly expressive cell clones / cell lines, and the efficient development of their culture processes, place even higher demands on the throughput and parallelism of bioreactors. Therefore, cell line screening, culture medium development, and process optimization all rely heavily on high-throughput bioreactor modules.

[0003] Compared to traditional stainless steel or glass bioreactors, disposable bioreactors offer numerous advantages, including simple operation, stable processes, short batch-to-batch preparation times, high production efficiency, no need for complex piping or other auxiliary facilities, no need for cleaning and sterilization, low production costs, and ease of validation. They are increasingly widely used in the development and production of modern biopharmaceuticals and have become a major trend in bioreactor development. Developing disposable, high-throughput bioreactor modules will significantly shorten the R&D cycle of biomanufacturing products and has broad application prospects.

[0004] The bioreactor module structure system is a device system that integrates hardware and software and efficient communication response for the initial small-scale culture of cells and microorganisms and the reliability screening and verification of process parameters. With the market promotion of cell immunotherapy, innovative macromolecular drugs, and synthetic biological products, the field of novel biomanufacturing is facing unprecedented opportunities, and bioreactors are being given a broader scope.

[0005] Existing parallel bio-fermentation systems are constrained by physical factors such as hardware scale and size. If a larger number of tanks are required, the electrical and piping connections between these tanks will consume significant laboratory personnel's time and increase the risk of incorrect connections. Furthermore, using reusable tanks poses potential risks regarding aseptic technique and contamination. Extensive manual operation is inconvenient for operators and makes it difficult to ensure the parallelism of the experimental process, introducing considerable uncertainty and risk into the experiment. Summary of the Invention

[0006] The main objective of this invention is to provide a bioreaction module structure and a parallel bioreaction system, thereby overcoming the shortcomings of the prior art.

[0007] To achieve the aforementioned objectives, the technical solution adopted by this utility model includes:

[0008] The first aspect of this utility model provides a bioreactor module structure, which includes a connecting base plate and a liquid addition assembly, a gas connector, and a reaction vessel integrated structure disposed on the connecting base plate. The reaction vessel integrated structure and the connecting base plate are capable of unresisted relative movement along the axial direction of the reaction vessel integrated structure. The reaction vessel integrated structure is at least used to provide a controllable environment for biological culture. The gas connector is connected to the reaction vessel integrated structure via a gas supply pipeline, and the liquid addition assembly is connected to the reaction vessel integrated structure via a liquid inlet pipeline.

[0009] The liquid addition assembly includes at least two sets of continuous liquid addition assemblies and at least three sets of intermittent liquid addition assemblies. The continuous liquid addition assembly includes a liquid storage tank and a peristaltic pump. Each liquid storage tank is connected to the integrated structure of the reaction vessel via a peristaltic pump and a liquid inlet pipe. The intermittent liquid addition assembly includes a liquid addition tank with a piston. Each liquid addition tank is connected to the integrated structure of the reaction vessel via a liquid inlet pipe.

[0010] A second aspect of this utility model provides a parallel bioreactor system, comprising: a reactor base, an electrical control component, a robotic arm, multiple reactor bases, and multiple bioreactor module structures; the electrical control component, the robotic arm, and the multiple reactor bases are fixedly mounted on the reactor base, and the multiple bioreactor module structures are detachably mounted on the reactor base. Each bioreactor module structure and a reactor base are configured to form a bioreactor unit. The robotic arm is used to perform liquid addition actions on the liquid addition components of the multiple bioreactor module structures. The electrical control component is electrically connected to the bioreactor module structures, the reactor bases, and the robotic arm.

[0011] Compared with the prior art, the advantages of this utility model include:

[0012] The bioreactor module structure proposed in this invention uses disposable, sterilized, pyrogen-free materials, which facilitates process testing and cultivation. After the experiment, no cleaning or disinfection is required, simplifying the experimental operation process. At the same time, the use of disposable materials avoids cross-contamination. In addition, the elimination of cleaning and disinfection significantly shortens the experimental time and improves experimental efficiency. The use of grouped consumables reduces the connection of external pipelines, thus reducing the risk of verification and other complications.

[0013] The bioreactor module structure proposed in this invention uses a deeply integrated bottom electromagnetic stirring and semiconductor temperature control to achieve stirring and temperature control of the reactor. Compared with the traditional top stirring method and electric heating and cooling water temperature control method, the structure is simpler and the upper space of the tank is large, which facilitates manual operation and observation.

[0014] The present invention proposes a bioreactor module structure with a multi-channel, small-capacity design, which can meet the requirements of small-scale laboratory culture and high-throughput screening. At the same time, it uses disposable, sterile, and pyrogen-free consumables for liquid culture, which makes it convenient for operators to quickly start the experiment.

[0015] The present invention proposes a bioreaction module structure that employs small-capacity culture, reduces reagent usage, and improves the economic efficiency of high-throughput experiments, reaction condition optimization experiments, reaction kinetic research experiments, and high-capacity screening.

[0016] This invention proposes a parallel bioreactor system that uses a motion platform (i.e., a robotic arm) for liquid addition. One liquid addition platform can complete the time-sharing liquid addition of several or even dozens of liquid addition cylinders. The system has a high degree of integration and is particularly suitable for high-throughput parallel bioreactor applications. Furthermore, this invention adopts a press-to-add liquid method, separating the liquid storage cylinder, pipeline, and liquid addition cylinder of the liquid inlet pipeline from the liquid addition power control system. This allows for easier design of the liquid inlet pipeline system into a disposable reaction system and external control, facilitating the integrated development of disposable bioreactors.

[0017] This invention proposes a parallel bioreactor system in which multiple reaction units operate under identical experimental conditions, ensuring consistency in experimental conditions. This consistency leads to more comparable experimental data, facilitating the analysis and comparison of results. Parallel experiments significantly improve experimental efficiency and shorten the experimental cycle. Furthermore, because the disposable bioreactor module structure contains multiple reaction units, high-throughput experiments can be achieved, enabling the completion of a large number of experiments in a short time, thus improving experimental efficiency.

[0018] This invention proposes a parallel bioreactor system in which a robotic arm is introduced into the reactor operation, greatly reducing manual operation steps and improving the parallelism of the reactors. At the same time, each reaction tank group is equipped with an independent liquid addition channel, which allows for more flexible parameter configuration and experimentation.

[0019] The parallel bioreactor system proposed in this invention adopts a compact design, occupies a small volume, and the equipment with multiple bioreactor modules can be placed in a two-person biosafety cabinet. Attached Figure Description

[0020] 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 recorded in this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a schematic diagram of the structure of a parallel bioreaction system provided in a typical embodiment of this utility model;

[0022] Figure 2 This is a side view of a parallel bioreaction system provided in a typical embodiment of this utility model;

[0023] Figure 3 This is a top view of a parallel bioreaction system provided in a typical embodiment of this utility model;

[0024] Figure 4 This is a schematic diagram of a bioreactor module structure provided in a typical embodiment of this utility model;

[0025] Figure 5 This is a schematic diagram of an integrated reaction vessel structure provided in a typical embodiment of this utility model;

[0026] Figure 6 This is a cross-sectional structural diagram of a bioreactor module structure and a reactor base combined in a typical embodiment of this utility model.

[0027] Figure 7 , Figure 8 This is a schematic diagram of the structure of the thermostatic holding base provided in a typical embodiment of this utility model;

[0028] Figure 9 This is a schematic diagram of the configuration structure of multiple constant temperature holding seats and an integrated water-cooled base provided in a typical embodiment of this utility model. Detailed Implementation

[0029] In view of the shortcomings of the prior art, the inventors of this case have proposed the technical solution of this utility model through long-term research and extensive practice.

[0030] The first aspect of this utility model provides a bioreactor module structure, which includes a connecting base plate and a liquid addition assembly, a gas connector, and a reaction vessel integrated structure disposed on the connecting base plate. The reaction vessel integrated structure and the connecting base plate are capable of unresisted relative movement along the axial direction of the reaction vessel integrated structure. The reaction vessel integrated structure is at least used to provide a controllable environment for biological culture. The gas connector is connected to the reaction vessel integrated structure via a gas supply pipeline, and the liquid addition assembly is connected to the reaction vessel integrated structure via a liquid inlet pipeline.

[0031] The liquid addition assembly includes at least two sets of continuous liquid addition assemblies and at least three sets of intermittent liquid addition assemblies. The continuous liquid addition assembly includes a liquid storage tank and a peristaltic pump. Each liquid storage tank is connected to the integrated structure of the reaction vessel via a peristaltic pump and a liquid inlet pipe. The intermittent liquid addition assembly includes a liquid addition tank with a piston. Each liquid addition tank is connected to the integrated structure of the reaction vessel via a liquid inlet pipe.

[0032] Furthermore, the integrated structure of the reaction vessel includes a reaction vessel body and pH monitoring electrode, temperature monitoring electrode, stirring paddle, DO electrode patch, exhaust filter, liquid inlet pipe, liquid outlet pipe and gas supply pipe integrated on the reaction vessel body. The liquid inlet pipe is used to connect to the liquid addition assembly, and the gas supply pipe is used to connect to the gas connector.

[0033] Furthermore, the reaction vessel body is also provided with an observation window that allows viewing of the interior of the reaction vessel body.

[0034] A second aspect of this utility model provides a parallel bioreactor system, comprising: a reactor base, an electrical control component, a robotic arm, multiple reactor bases, and multiple bioreactor module structures; the electrical control component, the robotic arm, and the multiple reactor bases are fixedly mounted on the reactor base, and the multiple bioreactor module structures are detachably mounted on the reactor base. Each bioreactor module structure and a reactor base are configured to form a bioreactor unit. The robotic arm is used to perform liquid addition actions on the liquid addition components of the multiple bioreactor module structures. The electrical control component is electrically connected to the bioreactor module structures, the reactor bases, and the robotic arm.

[0035] Furthermore, the reactor base includes a thermostatic holding seat and a stirring drive mechanism. The thermostatic holding seat is used to adjust the temperature of the reaction vessel body of the integrated reaction vessel structure, and the stirring drive mechanism is used to drive the stirring paddle of the integrated reaction vessel structure to rotate.

[0036] Furthermore, the constant temperature holding base itself encloses a receiving space, and at least the bottom of the reaction vessel body is correspondingly disposed in the receiving space. The reaction vessel body disposed in the receiving space is wrapped by the constant temperature holding base and thermally connected with the constant temperature holding base. The stirring drive mechanism is in drive cooperation with the stirring paddle in the integrated structure of the reaction vessel.

[0037] Furthermore, the stirring paddle of the integrated reaction vessel structure is a magnetic stirring paddle, and the stirring drive mechanism is connected to the magnetic stirring paddle via magnetic force.

[0038] Furthermore, the electrical control components are built into the reactor base.

[0039] Furthermore, the robotic arm is a multi-degree-of-freedom robotic arm.

[0040] Furthermore, the constant temperature holding base includes an inner temperature control base, a semiconductor refrigeration structure, a heat-conducting structure, an insulating sleeve, and an outer temperature control base. The inner temperature control base is sleeved inside the outer temperature control base. The insulating sleeve, the semiconductor refrigeration structure, and the heat-conducting structure are disposed between the inner temperature control base and the outer temperature control base. The semiconductor refrigeration structure is in direct thermal contact with the heat-conducting structure, and the semiconductor refrigeration structure is also in direct thermal contact with the inner temperature control base. The heat-conducting structure is in direct thermal contact with the outer temperature control base.

[0041] Furthermore, the insulating sleeve divides the annular space between the inner temperature control base and the outer temperature control base into multiple spaced positioning cavities, and the semiconductor cooling structure and the heat-conducting structure are disposed in the multiple positioning cavities.

[0042] Furthermore, the semiconductor cooling structure includes a plurality of semiconductor cooling chips, and the thermally conductive structure includes a plurality of thermally conductive chips. At least one of the semiconductor cooling chips and at least one of the thermally conductive chips are disposed in a positioning cavity and are in thermal contact.

[0043] Furthermore, the thermostatic holder is a conical cylindrical structure that is sealed at the bottom and open at the top.

[0044] Furthermore, the constant temperature holding seat is also provided with a clearance notch, and the observation window of the reaction vessel integrated structure placed in the containment space is exposed from the clearance notch.

[0045] Furthermore, the connecting base plate of the bioreactor module structure located on the reactor base is fitted with the reaction vessel integrated structure with a clearance. The reaction vessel integrated structure is suspended on the connecting base plate through a flange. After the reaction vessel body is installed, its bottom is in thermal contact with the thermostatic holding seat, and the weight is borne by the thermostatic holding seat.

[0046] The following will further explain the technical solution, its implementation process and principle in conjunction with the accompanying drawings and specific implementation examples. Unless otherwise specified, the electrical control components, reaction vessels, peristaltic pumps, gas connectors, semiconductor cooling chips, heat-conducting sheets, pH monitoring electrodes, temperature monitoring electrodes, magnetic stirrers, DO electrode patches, closed-loop motors and other components used in the embodiments of this utility model are all functional mechanisms known to those skilled in the art and can be obtained commercially. Their specific structures and product models are not limited here.

[0047] In a more typical implementation scheme, please refer to Figures 1-3 as well as Figure 4 A parallel bioreactor system includes multiple bioreactor module structures 100, reactor bases 200, robotic arms 400, multiple reactor bases 500, and electrical control components.

[0048] The system comprises an electrical control assembly, a robotic arm 400, and multiple reactor bases 500 fixedly mounted on a reactor base 200. Each bioreactor module 100 is detachably mounted on a reactor base 500, and each bioreactor module 100 and reactor base 500 are configured to form a bioreactor unit. The robotic arm 400 is used to perform liquid addition actions on the multiple bioreactor module 100s. The electrical control assembly is electrically connected to the robotic arm 400 and the multiple reactor bases 500, and is used to regulate the working status and parameters of the robotic arm 400 and reactor bases 500.

[0049] Specifically, the electrical control component can be directly fixed to the reactor base 200, encapsulated inside the reactor base 220, or integrated with the reactor base 200 as a single unit (i.e., the electrical control component and the reactor platform are integrated into a control cabinet). More specifically, the electrical control component can include a controller component, an electrical connection interface 210, and operation buttons / operation interfaces 220. The electrical connection interface 210 can be electrically connected to multiple bioreactor module structures, and the operation buttons / operation interfaces 220 are used to perform adjustment operations. It should be noted that the circuit structure and CNC program used in the electrical control component are commercially available. Here, the specific circuit structure and electrical control logic are limited. For example, the electrical control component can include a controller and related circuit boards, which are known to those skilled in the art.

[0050] Please see Figures 4-7The bioreactor module structure includes a connecting base plate 110 and a liquid addition assembly 120, a gas connector 130, and a reaction vessel integrated structure 140 disposed on the connecting base plate 110. The reaction vessel integrated structure 140 is confined on the connecting base plate 110, and the reaction vessel integrated structure 140 and the connecting base plate 110 can move relative to each other in one direction without resistance along the axial direction of the reaction vessel integrated structure 140. The liquid addition assembly 120 is connected to the reaction vessel integrated structure 140 via a liquid inlet pipe, and the gas connector 130 is connected to the reaction vessel integrated structure 140 via a gas delivery pipe.

[0051] Specifically, the liquid addition assembly 120 and the gas connector 130 can be fixed on the connecting base plate 110. The connecting base plate 110 is also provided with an installation port. The reaction vessel integrated structure 140 is disposed in the installation port. The diameter of the top part of the reaction vessel integrated structure 140 is larger than the inner diameter of the installation port, while the diameter of the bottom part of the reaction vessel integrated structure 140 is smaller than the diameter of the installation port. The reaction vessel integrated structure 140 cannot detach downward relative to the connecting base plate 110, but can detach upward relative to the connecting base plate 110. Of course, the reaction vessel integrated structure 140 can also be configured such that the diameter of the part near the top and bottom is larger than the inner diameter of the installation port, and the diameter of the middle part between the top and bottom is smaller than the inner diameter of the installation port.

[0052] Please refer to the following for details. Figure 5 , Figure 6 and Figure 7 The integrated structure 140 of the reaction vessel includes a reaction vessel body 1401, a liquid inlet pipe 1403, a gas supply pipe 1405, a temperature monitoring electrode 1405, a pH monitoring electrode 1406, an exhaust filter 1407, a sampling tube 1408, a liquid outlet pipe 1409, a stirring paddle 1411, and a DO electrode patch 1412. 1407, 1408, 1409, 1411, and DO electrode patch 1412 are integrated and mounted on the reaction vessel body 1401. The reaction vessel body 1401 is located within the mounting port of the connecting base plate 110 and can move freely in one direction relative to the connecting base plate 110 along the axial direction of the reaction vessel body 1401. Furthermore, the reaction vessel body 1401 is also provided with an observation window 1402 for viewing the interior of the reaction vessel body. More specifically, the reaction vessel body 1401 is connected to the liquid addition assembly 120 via the liquid inlet pipe 1403, and the reaction vessel body 1401 is connected to the gas connector 130 via the gas supply pipe 1405. It should be noted that the material of the reaction vessel body is medical-grade PC, which has passed USP Class VI and ISO 10993-5 cytotoxicity tests. Of course, the materials selected for other components also meet the corresponding requirements.

[0053] More specifically, the temperature monitoring electrode 1405, pH monitoring electrode 1406, exhaust filter 1407, sampling tube 1408, liquid outlet pipe 1409, stirring paddle 1411, and DO electrode patch 1412, as well as the liquid inlet pipe 1403, gas delivery pipe 1405, temperature monitoring electrode 1405, pH monitoring electrode 1406, exhaust filter 1407, sampling tube 1408, liquid outlet pipe 1409, stirring paddle 1411, and DO electrode patch 1412, and their fit and structure with the reaction vessel body 1401 are basically consistent with existing technologies and are not specifically limited here. The pH monitoring electrode 1406 is used to detect the reaction... The pH value of the liquid reaction system within the reaction tank body 1401 is monitored. A temperature monitoring electrode 1405 is used to detect the temperature of the liquid reaction system within the reaction tank body 1401. A DO electrode patch 1412 is used to detect the dissolved oxygen level of the liquid reaction system within the reaction tank body 1401. A stirring paddle 1411, in conjunction with a stirring drive mechanism, stirs the liquid reaction system within the reaction tank body 1401. These are all known to those skilled in the art. More specifically, the DO electrode patch 1412, in conjunction with an external fiber optic sensor, achieves dissolved oxygen detection. The external fiber optic sensor moves via a single-axis platform, enabling dissolved oxygen monitoring of multiple reactors. Specifically, an exhaust filter is preferably installed on the tank cover 1413 of the reaction tank body 1401. The exhaust filter is used to filter out other substances discharged from the reaction tank body 1401. This is a conventional setup in the art, and exhaust filters are commercially available. Specifically, the integrated reaction tank structure 140 may include multiple liquid inlet pipes and gas delivery pipes to meet different liquid addition process requirements within the reaction tank body. Specifically, by integrating the liquid inlet pipeline and the gas supply pipeline onto the reaction vessel integrated structure 140, liquid addition and gas supply can be achieved simply by manual placement and connection, making it convenient for personnel to operate.

[0054] Specifically, the reactor base 500 includes a thermostatic holding seat 510 and a stirring drive mechanism 520. The thermostatic holding seat 510 is used to adjust the temperature of the reaction vessel body 1401 of the reaction vessel integrated structure 140, and the stirring drive mechanism 520 is used to drive the stirring paddle 1411 in the reaction vessel integrated structure 140 to rotate, so as to achieve stirring of the liquid reaction system in the reaction vessel body 1401.

[0055] It should be noted that when the bioreactor module structure 100 is set on the reactor base 200, the connecting base plate 110 is fixed relative to the reactor base 200, and the reaction vessel body 1401 of the reaction vessel integrated structure 140 is correspondingly set in the receiving space of the constant temperature holding seat 510. The reaction vessel body 1401 and the connecting base plate 110 are fitted with a clearance. Of course, the reactor base and the constant temperature holding seat can also be integrated with interconnected water cooling structures to cool multiple reaction vessel integrated structures 140. It should be noted that the water cooling structure in the constant temperature holding seat is set independently, while the water cooling structure in the reactor base is integrated, that is, the water cooling structures in multiple constant temperature holding seats are respectively connected to the water cooling structure in the reactor base.

[0056] More specifically, the thermostatic holding base 510 encloses a receiving space, and is mounted on 520. At least the bottom of the reaction vessel body 1401 is correspondingly positioned within the receiving space. The stirring drive mechanism 520 is in transmission cooperation with the stirring paddle 1411 inside the reaction vessel body 1401. More specifically, the thermostatic holding base 510 has a cylindrical structure. The reaction vessel body 1401, positioned within the receiving space, is enclosed by the thermostatic holding base 510 and thermally conductively connected with it. Furthermore, the thermostatic holding base 510 is provided with a clearance notch, through which an observation window 1402 on the reaction vessel body 1401, positioned within the receiving space, protrudes. Specifically, as known to those skilled in the art, the thermostatic holding base 510 may also be provided with a patch detection hole 501, etc.

[0057] Specifically, at least the bottom part of the reaction vessel body 1401 is located within the containment space and is wrapped by the thermostatic holder 510. Understandably, the thermostatic holder 510 is attached to / in contact with the reaction vessel body 1401, or it can be directly fixedly connected.

[0058] For more details, please see Figure 8 and Figure 9 The constant temperature holding base 510 includes an inner temperature control base 511, a semiconductor cooling structure 512, a heat conduction structure 513, an insulating sleeve 514, and an outer temperature control base 515. The inner temperature control base 511 is fitted inside the outer temperature control base 515. The insulating sleeve 514, the semiconductor cooling structure 512, and the heat conduction structure 513 are disposed between the inner temperature control base 511 and the outer temperature control base 515. The semiconductor cooling structure and the heat conduction structure 513 are in direct thermal contact. The semiconductor cooling structure 512 is also in direct thermal contact with the inner temperature control base 511. The heat conduction structure 513 is in direct thermal contact with the outer temperature control base 515.

[0059] Specifically, the insulating sleeve 514 is mainly used to prevent short circuits between the inner temperature control base 511 and the outer temperature control base 515. As a preferred embodiment, the insulating sleeve 514 divides the annular space between the inner temperature control base and the outer temperature control base 515 into multiple spaced positioning cavities. The semiconductor cooling structure 512 and the heat-conducting structure 513 are disposed in multiple positioning cavities. Of course, the insulating sleeve 514 can be an annular structure with multiple hollow structures, and the semiconductor cooling structure 512 and the heat-conducting structure 513 are correspondingly disposed in the hollow structures of the insulating sleeve 514. Specifically, the semiconductor cooling structure 512 includes multiple semiconductor cooling chips, and the heat-conducting structure 513 includes multiple heat-conducting chips. The multiple semiconductor cooling chips and the multiple heat-conducting chips are all spaced apart along the circumference of the constant temperature holding base 510. A semiconductor cooling chip and a heat-conducting chip are disposed in a positioning cavity and are in thermal contact. As mentioned above, the semiconductor cooling chip is in direct contact with the inner temperature control base 511, and the heat-conducting chip is in direct contact with the outer temperature control base 515.

[0060] Specifically, both the inner temperature control base 511 and the outer temperature control base 515 are made of high thermal conductivity materials known in the art, facilitating heat conduction between the inner temperature control base 511 and the reaction vessel body 1401, as well as between the outer temperature control base 515 and the external environment. The insulating sleeve 514 is made of a high thermal resistance material known in the art. Specifically, multiple thermoelectric coolers and multiple heat-conducting sheets are circumferentially spaced to ensure uniformity of cooling and heating. During heating, the thermoelectric coolers conduct heat from the outer temperature control base 515 to the inner temperature control base 511, and heat is conducted from the environment to the outer temperature control base 515. During cooling, the thermoelectric coolers conduct heat from the inner temperature control base 511 to the heat-conducting sheets, and the heat-conducting sheets transfer heat to the outer temperature control base 515. The outer temperature control base 515 dissipates heat through surface convection.

[0061] Please refer to the following for details. Figure 9 The thermostatic holding base 510 in this invention uses a semiconductor cooling chip for cooling. It achieves precise temperature control inside the tank through dual control of a built-in temperature sensor and a tank temperature sensor. Each tank is independent of the others. At the same time, multiple thermostatic holding bases 510 are installed on an integrated water-cooled base 600 and cooperate with the integrated water-cooled base 600 for heat conduction. The integrated water-cooled base 600 is installed on the reactor base. The heat of the multiple thermostatic holding bases 510 is carried away by the integrated water-cooled base 600. The temperature of the integrated water-cooled base 600 is maintained by water cooling, which is more efficient than the air cooling of the thermostatic holding base shell and can more effectively control the temperature inside the tank, especially the low temperature control.

[0062] It should be noted that the structure of the semiconductor cooling chip and the heat-conducting chip and the principle of their temperature regulation are known to those skilled in the art, and their specific structures are not limited here.

[0063] Specifically, the reaction vessel integrated structure 140 achieves precise control of the liquid temperature inside the reaction vessel body 1401 through the constant temperature holding seat 510 wrapped around the reaction vessel body 1401, and the temperature monitoring electrode 1405 located inside the reaction vessel body 1401 achieves precise detection of the temperature of the liquid reaction system inside the reaction vessel body 1401.

[0064] Specifically, the stirring paddle 1411 is a magnetic stirring paddle, and the stirring drive mechanism 520 is a closed-loop motor. The closed-loop motor is built into the reactor base 500 and is correspondingly set at the bottom of the reaction tank body 140. The closed-loop motor is connected to the magnetic stirring paddle through magnetic force and drives the magnetic stirring paddle located inside the reaction tank body 1401 to stir according to the process speed.

[0065] In a first embodiment of this utility model, the liquid addition assembly includes at least two sets of continuous liquid addition assemblies and at least three sets of intermittent liquid addition assemblies. The continuous liquid addition assembly includes a storage tank and a peristaltic pump. Each storage tank is connected to the reaction tank body via a peristaltic pump and an inlet pipe. The intermittent liquid addition assembly includes a liquid addition cylinder with a piston. Each liquid addition cylinder is connected to the reaction tank body via an inlet pipe. The peristaltic pump is used to drive the liquid in the storage tank to enter the reaction tank body 1401 of the integrated reaction tank structure along the inlet pipe. For example, the liquid addition assembly of each bioreactor unit may include two storage tanks and three liquid addition cylinders with pistons. The two storage tanks and three liquid addition cylinders with pistons form a five-way liquid inlet with the reaction tank body. The two peristaltic pumps drive the liquid addition to achieve continuous liquid addition in the reaction tank, which can cover liquid addition processes such as continuous feeding of culture medium and pH control. The liquid addition cylinder is driven by a robotic arm to achieve liquid addition, thereby achieving high-precision non-continuous liquid addition.

[0066] Specifically, the peristaltic pump can be fixedly mounted on the reactor base 200. The peristaltic pump can also be connected to an electrical control assembly, whose operating status is controlled by the electrical control assembly. It should be noted that the peristaltic pump is commercially available, and its specific structure and product model are not limited here.

[0067] Specifically, the robotic arm 400 is used to perform push-pull actions on the piston rod of the liquid dispensing cylinder. More specifically, the robotic arm 400 is a multi-degree-of-freedom robotic arm 400, which performs push-pull actions on the piston rod of the liquid dispensing cylinder of multiple bioreactor module structures 100 to achieve the transfer and dispensing of liquid materials. It should be noted that the robotic arm 400 has a built-in precision photoelectric encoder, which can provide real-time feedback on the angle of the robotic arm, thereby sensing the position of the robotic arm's main shaft. For example, the robotic arm can be a three-axis, four-axis, or six-axis robotic arm known in the art, and its specific structure and equipment model are not limited here.

[0068] The bioreactor module structure proposed in this invention uses disposable, sterilized, pyrogen-free materials, which facilitates process testing and cultivation. After the experiment, no cleaning or disinfection is required, simplifying the experimental operation process. At the same time, the use of disposable materials avoids cross-contamination. In addition, the elimination of cleaning and disinfection significantly shortens the experimental time and improves experimental efficiency. The use of grouped consumables reduces the connection of external pipelines, thus reducing the risk of verification and other complications.

[0069] The bioreactor module structure proposed in this invention uses a deeply integrated bottom electromagnetic stirring and semiconductor temperature control to achieve stirring and temperature control of the reactor. Compared with the traditional top stirring method and electric heating and cooling water temperature control method, the structure is simpler and the upper space of the tank is large, which facilitates manual operation and observation.

[0070] The present invention proposes a bioreactor module structure with a multi-channel, small-capacity design, which can meet the requirements of small-scale laboratory culture and high-throughput screening. At the same time, it uses disposable, sterile, and pyrogen-free consumables for liquid culture, which makes it convenient for operators to quickly start the experiment.

[0071] The present invention proposes a bioreaction module structure that employs small-capacity culture, reduces reagent usage, and improves the economic efficiency of high-throughput experiments, reaction condition optimization experiments, reaction kinetic research experiments, and high-capacity screening.

[0072] This invention proposes a parallel bioreactor system that uses a motion platform (i.e., a robotic arm) for liquid addition. One liquid addition platform can complete the time-sharing liquid addition of several or even dozens of liquid addition cylinders. The system has a high degree of integration and is particularly suitable for high-throughput parallel bioreactor applications. Furthermore, this invention adopts a press-to-add liquid method, separating the liquid storage cylinder, pipeline, and liquid addition cylinder of the liquid inlet pipeline from the liquid addition power control system. This allows for easier design of the liquid inlet pipeline system into a disposable reaction system and external control, facilitating the integrated development of disposable bioreactors.

[0073] This invention proposes a parallel bioreactor system in which multiple reaction units operate under identical experimental conditions, ensuring consistency in experimental conditions. This consistency leads to more comparable experimental data, facilitating the analysis and comparison of results. Parallel experiments significantly improve experimental efficiency and shorten the experimental cycle. Furthermore, because the disposable bioreactor module structure contains multiple reaction units, high-throughput experiments can be achieved, enabling the completion of a large number of experiments in a short time, thus improving experimental efficiency.

[0074] This invention proposes a parallel bioreactor system in which a robotic arm is introduced into the reactor operation, greatly reducing manual operation steps and improving the parallelism of the reactors. At the same time, each reaction tank group is equipped with an independent liquid addition channel, which allows for more flexible parameter configuration and experimentation.

[0075] The parallel bioreactor system proposed in this invention adopts a compact design, occupies a small volume, and the equipment with multiple bioreactor modules can be placed in a two-person biosafety cabinet.

[0076] It should be understood that the above embodiments are merely illustrative of the technical concept and features of this utility model, and are intended to enable those skilled in the art to understand the content of this utility model and implement it accordingly. They should not be construed as limiting the scope of protection of this utility model. All equivalent changes or modifications made in accordance with the spirit and essence of this utility model should be included within the scope of protection of this utility model.

Claims

1. A bioreactor module structure, characterized in that, include: The system includes a connecting base plate and a liquid addition assembly, a gas connector, and an integrated reaction vessel structure disposed on the connecting base plate. The integrated reaction vessel structure and the connecting base plate are capable of unimpeded relative movement along the axial direction of the integrated reaction vessel structure. The integrated reaction vessel structure is at least used to provide a controllable environment for biological culture. The gas connector is connected to the integrated reaction vessel structure via a gas supply pipeline, and the liquid addition assembly is connected to the integrated reaction vessel structure via a liquid inlet pipeline. The liquid addition assembly includes at least two sets of continuous liquid addition assemblies and at least three sets of intermittent liquid addition assemblies. The continuous liquid addition assembly includes a liquid storage tank and a peristaltic pump. Each liquid storage tank is connected to the integrated structure of the reaction vessel via a peristaltic pump and a liquid inlet pipe. The intermittent liquid addition assembly includes a liquid addition tank with a piston. Each liquid addition tank is connected to the integrated structure of the reaction vessel via a liquid inlet pipe.

2. The bioreactor module structure according to claim 1, characterized in that: The integrated structure of the reaction vessel includes a reaction vessel body and pH monitoring electrode, temperature monitoring electrode, stirring paddle, DO electrode patch, exhaust filter, liquid inlet pipe, liquid outlet pipe and gas supply pipe integrated on the reaction vessel body. The liquid inlet pipe is used to connect to the liquid addition assembly, and the gas supply pipe is used to connect to the gas connector.

3. The bioreactor module structure according to claim 2, characterized in that: The reaction vessel body is also provided with an observation window that allows a view of the interior of the reaction vessel body.

4. A parallel bioreaction system, characterized in that, include: The system comprises a reactor base, an electrical control assembly, a robotic arm, multiple reactor bases, and multiple bioreactor module structures as described in any one of claims 1-3; the electrical control assembly, the robotic arm, and the multiple reactor bases are fixedly mounted on the reactor base, the multiple bioreactor module structures are detachably mounted on the reactor base, each bioreactor module structure and a reactor base are configured to form a bioreactor unit, the robotic arm is used to perform liquid addition actions on the liquid addition assemblies of the multiple bioreactor module structures, and the electrical control assembly is electrically connected to the bioreactor module structures, the reactor bases, and the robotic arm.

5. The parallel bioreaction system according to claim 4, characterized in that: The reactor base includes a thermostatic holding seat and a stirring drive mechanism. The thermostatic holding seat is used to adjust the temperature of the reaction vessel body of the integrated reaction vessel structure, and the stirring drive mechanism is used to drive the stirring paddle of the integrated reaction vessel structure to rotate.

6. The parallel bioreaction system according to claim 5, characterized in that: The constant temperature holding base itself encloses a receiving space, and at least the bottom of the reaction vessel body is correspondingly disposed in the receiving space. The reaction vessel body disposed in the receiving space is wrapped by the constant temperature holding base and thermally connected with the constant temperature holding base. The stirring drive mechanism is in drive cooperation with the stirring paddle in the integrated structure of the reaction vessel.

7. The parallel bioreaction system according to claim 6, characterized in that: The stirring paddle of the integrated reaction vessel structure is a magnetic stirring paddle, and the stirring drive mechanism is connected to the magnetic stirring paddle by magnetic force.

8. The parallel bioreaction system according to claim 6, characterized in that: The electrical control components are built into the reactor base.

9. The parallel bioreaction system according to claim 6, characterized in that: The robotic arm is a multi-degree-of-freedom robotic arm.

10. The parallel bioreaction system according to claim 6, characterized in that: The constant temperature holding base includes a temperature-controlled inner base, a semiconductor refrigeration structure, a heat-conducting structure, an insulating sleeve, and a temperature-controlled outer base. The temperature-controlled inner base is sleeved inside the temperature-controlled outer base. The insulating sleeve, the semiconductor refrigeration structure, and the heat-conducting structure are disposed between the temperature-controlled inner base and the temperature-controlled outer base. The semiconductor refrigeration structure is in direct thermal contact with the heat-conducting structure, and the semiconductor refrigeration structure is also in direct thermal contact with the temperature-controlled inner base. The heat-conducting structure is in direct thermal contact with the temperature-controlled outer base.

11. The parallel bioreaction system according to claim 10, characterized in that: The insulating sleeve divides the annular space between the inner temperature control base and the outer temperature control base into multiple spaced positioning cavities, and the semiconductor cooling structure and the heat-conducting structure are disposed in the multiple positioning cavities.

12. The parallel bioreaction system according to claim 11, characterized in that: The semiconductor cooling structure includes multiple semiconductor cooling chips, and the thermally conductive structure includes multiple thermally conductive chips. At least one of the semiconductor cooling chips and at least one of the thermally conductive chips are disposed in a positioning cavity and are in thermal contact.

13. The parallel bioreaction system according to claim 10, characterized in that: The thermostatic holder is a conical cylindrical structure that is sealed at the bottom and open at the top.

14. The parallel bioreaction system according to claim 13, characterized in that: The constant temperature holding seat is also provided with a clearance notch, and the observation window of the integrated structure of the reaction vessel placed in the containment space is exposed from the clearance notch.

15. The parallel bioreaction system according to claim 10, characterized in that: The connecting substrate of the bioreactor module structure located on the reactor base is fitted with the integrated structure of the reaction vessel with a clearance.

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