Carbon dioxide gas supply device for cell culture
By designing a helical assembly and a gas concentration detection mixing device, the problem of difficulty in adjusting the gas mixing concentration in existing technologies has been solved, achieving efficient and energy-saving gas mixing effects that can meet the culture needs of different cells.
Patent Information
- Application Number
- CN202511016721.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-23
- Publication Date
- 2025-10-24
- Estimated Expiration
- 2045-07-23
AI Technical Summary
Existing cell culture chamber gas supply systems are difficult to precisely adjust the gas mixing concentration. Static mixing is time-consuming and inefficient, while dynamic mixing requires an external power unit, increasing the equipment size and making it unsuitable for compact mixing chambers.
The mixing device, which employs a spiral assembly design, achieves precise and uniform gas mixing by adjusting the angle between the moving and fixed spiral bodies, combined with a gas concentration detection and heating module.
It enables precise adjustment of the gas mixing concentration required for different cells, improves mixing efficiency, reduces energy consumption, and adapts to the needs of compact mixing chambers.
Smart Images

Figure CN120829833A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of medical equipment, in particular to a carbon dioxide gas supply device for cell culture. BACKGROUND
[0002] In the field of cell culture and biomedical research, creating a suitable growth environment for cells is a key factor to ensure the success of experiments and the reliability of results. Among them, carbon dioxide as a key factor in cell culture process, plays a crucial role in physiological processes such as cell metabolic activity, acid-base balance regulation and cell signal transduction.
[0003] At present, the more flexible gas supply mode in the cell culture box generally uses double gas sources, that is, CO2, N2 and air (or O2) are used as gas sources to supply mixed gas into the culture box, which can meet the stringent requirements of in vitro fertilization (IVF) embryo cells and stem cell culture, and has a wider application range.
[0004] The Chinese patent with application number 202210421460.6 discloses a gas supply system for a cell culture box, which includes a gas source module, an air inlet control module, a gas mixing module and a culture chamber module connected in sequence. The gas source module includes a CO2 gas source and an N2 gas source. The air inlet control module includes a first flow control device and a second flow control device connected with the CO2 gas source and the N2 gas source respectively. The gas mixing module includes a premixing chamber, a CO2 concentration sensor, an O2 concentration sensor arranged in the premixing chamber and a pressure relief valve for discharging excess gas. The culture chamber module includes a plurality of corresponding culture chambers and gas supply pumps. The gas supply pumps are used to send the mixed gas from the gas mixing module into the culture chambers and return to the gas mixing module to complete the circulation. The system also includes a central controller, which can simplify the system, supply gas to multiple culture chambers at the same time, use internal gas circulation, have high concentration control stability and low gas consumption.
[0005] However, although the above-mentioned patent technology has the ability to supply gas to multiple culture chambers at the same time, the existing double-gas-source culture box gas supply system still has many deficiencies in actual application. On the one hand, when supplying gas to different types of cells, some cell types have very high requirements for the accuracy of gas mixing concentration, and the existing device is difficult to finely adjust the accuracy of gas mixing concentration. On the other hand, the gas supply system in the prior art usually uses static mixing or dynamic mixing in the gas mixing process. If the static mixing method only relies on natural diffusion of gas, it takes a long time to achieve uniform mixing of gas, and the mixing effect is poor when the gas density difference is small, which may cause gas stratification. Although the dynamic mixing method has relatively high mixing efficiency, dynamic mixing usually needs to be connected with a power device, which increases energy consumption. At the same time, the introduction of mechanical parts increases the volume of the equipment, which is difficult to adapt to compact mixing cavities. SUMMARY
[0006] The present application aims to provide a carbon dioxide gas supply device for cell culture to solve the technical problems raised in the background.
[0007] To achieve the above object, the present application provides the following technical solutions: A carbon dioxide gas supply device for cell culture, comprising a shell, the shell is provided with a mixing device, gas enters the mixing device through the gas inlet pipe, the mixed gas enters the heating module through the gas outlet pipe, and the mixed gas enters the cell incubator after being heated by the heating module; The inside of the mixing device is symmetrically provided with a spiral assembly, which comprises fixed spirals and movable spirals distributed alternately, the fixed spirals are fixedly connected with the mixing device, and the movable spirals are rotatably connected with the fixed spirals; The lower part of the spiral assembly is provided with a pressure receiving assembly, which is drivingly connected with the movable spiral, by adjusting the pressure receiving degree of the pressure receiving assembly, the included angle between the movable spiral and the fixed spiral is changed to adapt to the gas supply requirements of different cells.
[0008] Preferably, the mixing device comprises: A body fixedly arranged inside the shell; A premixing cavity located at the bottom region of the body, and the pressure receiving assembly is located inside the premixing cavity; A mixing part located above the premixing cavity, and the spiral assembly is located inside the mixing part; A communication hole arranged at the junction of the premixing cavity and the mixing part, and an adjusting member is arranged on the communication hole to adjust the flow rate of the gas entering the mixing part through the communication hole.
[0009] Preferably, the mixing part comprises: A first mixing cavity and a second mixing cavity, which are symmetrically arranged above the premixing cavity and are both provided with a spiral assembly inside; A through hole, the first mixing cavity and the second mixing cavity are communicated with each other through the through hole, and a gas concentration detection unit is arranged inside the through hole.
[0010] Preferably, the movable spiral is rotatably connected with the fixed spiral through a rotating cylinder, the rotating cylinder is provided with a rotating groove, and the rotating cylinder is drivingly connected with the pressure receiving assembly through the rotating groove.
[0011] Preferably, the pressure receiving assembly comprises: A movable part arranged inside the premixing cavity and slidingly connected with the premixing cavity; A pressing part arranged at the top of the movable part, one end of the pressing part located in the rotating cylinder is provided with a pressure block, and the pressure block is in contact with the rotating groove; An elastic member is arranged at the bottom of the movable part to buffer the pressure received by the pressing part.
[0012] Preferably, the pitch of the spiral groove in the first mixing cavity is greater than the pitch of the spiral groove in the second mixing cavity.
[0013] Preferably, the heating module comprises: A heating seat connected to the gas outlet pipe, and a heat conduction cavity inside the heating seat for heating the mixed gas; A heating unit arranged in the heating seat to provide heat for the heat conduction cavity; A temperature measuring element arranged inside the heat conduction cavity to detect the temperature change of the mixed gas when heated; A gas outlet arranged on the outside of the heating seat and in communication with the heat conduction cavity, through which the heated mixed gas enters the inside of the cell incubator.
[0014] Preferably, a filter is arranged on the gas outlet pipe to filter impurities in the mixed gas.
[0015] Preferably, the gas outlet end of the gas inlet pipe enters the premixing cavity through a proportional valve, and the gas is preliminarily mixed in the premixing cavity.
[0016] Preferably, a controller is arranged inside the shell, and the electrical elements inside the shell are electrically connected to the controller.
[0017] Technical effects and advantages of the present application: 1. The present application meets the precision requirements of different cells for gas mixing concentration by arranging the pressure receiving assembly and the mixing part. The mixing part adopts the first and second mixing cavities arranged symmetrically and with spiral assemblies, the spiral assemblies are composed of fixed and movable spiral bodies, the movable spiral body is deflected by pressure change control, the included angle between the movable spiral body and the fixed spiral body is changed to adapt to different mixing requirements. For cells with low mixing degree requirements, a certain included angle is maintained to ensure high gas flowability; for cells with high requirements, the included angle is expanded to improve the mixing effect, and even the movable spiral body is reversed by adjusting the valve to realize dynamic mixing. Due to the difference in pitch of the spiral grooves of the two mixing cavities, the second mixing cavity is more uniform, effectively avoiding the problem of uneven mixing. BRIEF DESCRIPTION OF DRAWINGS
[0018] Figure 1 It is a schematic diagram of the main structure of the present application; Figure 2 It is another perspective view of the main structure of the present application; Figure 3 It is a schematic diagram of the internal structure of the shell of the present application; Figure 4 It is a first cross-sectional view of the heating module of the present application; Figure 5The second cross-section schematic view of the heating module of the present application; Figure 6 The structural schematic view of the mixing device of the present application; Figure 7 The front structural schematic view of the mixing device of the present application; Figure 8 The structural schematic view of the spiral assembly of the present application; Figure 9 The structural schematic view of the rotating groove of the present application.
[0019] In the figure: 1, the shell; 2, the mixing device; 201, the body; 202, the premixing cavity; 203, the mixing part; 2031, the first mixing cavity; 2032, the second mixing cavity; 2033, the through hole; 204, the communication hole; 3, the spiral assembly; 301, the fixed spiral body; 302, the movable spiral body; 303, the rotating cylinder; 304, the rotating groove; 4, the pressure receiving assembly; 401, the movable part; 402, the extrusion part; 403, the elastic member; 5, the air inlet pipe; 6, the air outlet pipe; 7, the filter; 8, the heating module; 801, the heating seat; 802, the heat conduction cavity; 803, the temperature measuring element; 804, the air outlet; 9, the controller. DETAILED DESCRIPTION
[0020] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.
[0021] Embodiment one Referring to Figures 1 to 6 As shown in the figure, the present application proposes a carbon dioxide gas supply device for cell culture, which comprises a shell 1, the shell 1 is internally provided with a mixing device 2, and the mixing device 2 is internally and symmetrically arranged with a spiral assembly 3.
[0022] Referring to Figure 6 As shown in the figure, the mixing device 2 comprises a body 201, the body 201 is internally and symmetrically provided with a first mixing cavity 2031 and a second mixing cavity 2032, the two mixing cavities are both configured with the spiral assembly 3, and the two cavities are in mutual communication through a through hole 2033.
[0023] Referring toFigure 3 As shown, the bottom region of the body 201 is provided with an air inlet pipe 5, which is provided with a proportional valve (including an electromagnetic valve) at the connection with the body 201, for regulating the proportion of gas flow. The outer side of the body 201 is provided with an air outlet pipe 6 in communication with the second mixing chamber 2032, and the end of the air outlet pipe 6 extending out of the shell 1 is connected with a heating module 8. The outer side of the air outlet pipe 6 is further provided with a filter 7 for purifying the mixed gas.
[0024] Referring to Figures 3 to 5 As shown, the heating module 8 specifically includes a heating seat 801, which is tightly connected with the air outlet pipe 6 and internally provided with a heat conduction chamber 802 for heating the mixed gas.
[0025] The heating seat 801 is further provided with a heating unit for providing necessary heat for the heat conduction chamber 802. The heat conduction chamber 802 is internally provided with a temperature measuring element 803 for real-time monitoring of the temperature change of the mixed gas during the heating process.
[0026] The outer side of the heating seat 801 is provided with an air outlet 804 in communication with the heat conduction chamber 802, through which the heated mixed gas enters the inside of the cell incubator.
[0027] In addition, the shell 1 is internally provided with a controller 9, and all the electrical elements in the shell 1 are electrically connected with the controller 9. The controller 9 is connected with the heating unit through wires to control the heating process.
[0028] During use of the device, after power-on, carbon dioxide and oxygen enter the proportional valve (electromagnetic valve) through the air inlet pipe 5 on the shell 1. After proportional adjustment by the electromagnetic valve, the gas flows into the first mixing chamber 2031 in the body 201. In the first mixing chamber 2031, the gas is mixed along the spiral assembly 3, and then enters the second mixing chamber 2032 through the through hole 2033, and is mixed again by the spiral assembly 3 in the second mixing chamber 2032 to ensure the uniformity of the gas mixing. The mixed gas flows out through the air outlet pipe 6 at the bottom region of the body 201 and is filtered by the filter 7. Then, the mixed gas reaches the mixed gas inlet of the heating module 8, and the mixed gas flows into the heat conduction chamber 802 inside through the mixed gas inlet, and the mixed gas is heated by the heat conduction chamber 802. The heated gas flows out along the air outlet hole and enters the cell incubator.
[0029] It should be noted that the heat conduction chamber 802 is internally provided with a temperature measuring element 803 (temperature sensor) for real-time monitoring of the temperature of the mixed gas in the heat conduction chamber 802. If the temperature of the mixed gas in the heat conduction chamber 802 deviates from the preset range, the temperature of the inflowing gas is accurately controlled by adjusting the temperature of the heating unit to meet the needs of cell culture.
[0030] Example Two Although the above-mentioned embodiments realize the mixed gas supply operation, there are still many deficiencies in the mixing of gas. On the one hand, when different types of cells are supplied with gas, some cells have high requirements for the accuracy of gas mixing concentration, and it is difficult to finely adjust. On the other hand, the existing gas mixing methods have static and dynamic two kinds. Static mixing relies on natural diffusion, which takes a long time, and the mixing effect is poor when the gas density difference is small, and it is easy to stratify; dynamic mixing has high efficiency, but needs to connect external power devices to increase energy consumption, and introduces mechanical parts to increase the volume of the equipment, which is difficult to adapt to compact cavities. In view of this, technical improvements are made on the basis of Embodiment One, and the improved technical scheme is as follows: Referring to Figures 1 to 9 A carbon dioxide gas supply device for cell culture, comprising a shell 1, the shell 1 is provided with a mixing device 2.
[0031] Referring to Figures 6 to 9 The mixing device 2 comprises a body 201, which is located inside the shell 1; the bottom area of the body 201 is provided with a premixing cavity 202, the upper side of the premixing cavity 202 is provided with a mixing part 203, and the junction of the premixing cavity 202 and the mixing part 203 is provided with a communication hole 204. The gas in the premixing cavity 202 enters the mixing part 203 through the communication hole 204.
[0032] The gas outlet end of the gas inlet pipe 5 is connected with the premixing cavity 202, the gas enters the premixing cavity 202 through the proportional valve on the gas inlet pipe 5, and is preliminarily mixed by the inside of the premixing cavity 202, and then enters the mixing part 203 through the communication hole 204, and is formally mixed by the mixing part 203.
[0033] An adjusting valve is arranged at the communication hole 204, which is used to adjust the opening size of the communication hole 204. Adjusting the opening size of the communication hole 204 through the adjusting valve belongs to the prior art, and will not be described in detail here.
[0034] Referring to Figure 7 The mixing part 203 comprises a first mixing cavity 2031 and a second mixing cavity 2032, which are symmetrically arranged above the premixing cavity 202, and each is provided with a spiral assembly 3 inside.
[0035] Referring to Figure 7 The first mixing cavity 2031 and the second mixing cavity 2032 are communicated with each other through a through hole 2033, and a gas concentration detection unit is arranged in the through hole 2033. The gas concentration detection unit comprises a concentration sensor for detecting the concentration of the mixed gas.
[0036] Referring to Figures 6 to 9As shown, the spiral assembly 3 comprises fixed spirals 301 and movable spirals 302 arranged alternately, the fixed spirals 301 are fixedly connected with the body 201, and the movable spirals 302 are rotationally connected with the fixed spirals 301.
[0037] When the movable spirals 302 and the fixed spirals 301 are in the staggered state, the gas is divided and mixed at the joint of the movable spirals 302 and the fixed spirals 301 during the gas flowing through the joint, and the mixing effect of the gas is improved through the violent radial mixing and reverse rotation.
[0038] Referring to Figures 6 to 9 As shown, the movable spirals 302 are rotationally connected with the fixed spirals 301 through the rotating cylinder 303, the rotating cylinder 303 is provided with a rotating groove 304 on the outer wall, and the rotating cylinder 303 is provided with a pressure receiving assembly 4 inside and in transmission connection with the rotating groove 304.
[0039] The pitch of the rotating groove 304 located in the first mixing chamber 2031 is greater than the pitch of the rotating groove 304 located in the second mixing chamber 2032.
[0040] Referring to Figure 7 As shown, the pressure receiving assembly 4 is arranged in the premixing chamber 202, and the pressure receiving assembly 4 comprises a movable part 401 in sliding connection with the premixing chamber 202, the bottom of the movable part 401 is provided with an elastic member 403 for buffering the pressure received by the extrusion part 402, and the top of the movable part 401 is provided with the extrusion part 402, one end of the extrusion part 402 extending into the rotating cylinder 303 is provided with a pressure block connected with the rotating groove 304.
[0041] In use, the carbon dioxide and the oxygen enter the proportional valve through the respective corresponding gas inlet pipes 5, and the carbon dioxide and the oxygen enter the premixing chamber 202 at the corresponding flow ratio through the proportional adjustment of the proportional valve, and then enter the first mixing chamber 2031 and the second mixing chamber 2032 through the regulating part after the preliminary mixing in the premixing chamber 202, so as to ensure the uniformity of the gas mixing.
[0042] It should be noted that the carbon dioxide and the oxygen mainly concentrate in the upper half area of the premixing chamber 202, i.e. the space above the movable part 401, after entering the premixing chamber 202.
[0043] After the carbon dioxide and the oxygen enter the premixing chamber 202, the pressure inside the premixing chamber 202 is adjusted by controlling the adjustment of the regulating part, so that the position of the movable part 401 inside the premixing chamber 202 changes, and the movable part 401 drives the movable spirals 302 to deflect through the extrusion part 402 when moving, so as to change the included angle between the movable spirals 302 and the fixed spirals 301. The specific action is as follows: When the pressure inside the premixing cavity 202 gradually increases, the gas pressure pushes the movable part 401 downward, and the movable part 401 drives the extrusion part 402 to move downward. Since the movable part 401 is in a limiting sliding connection with the premixing cavity 202, and the movable spiral body 302 is in a rotating connection with the fixed spiral body 301 through the rotating cylinder 303, during the downward movement of the extrusion part 402, the pressing block on the extrusion part 402 is extruded with the rotating groove 304 on the rotating cylinder 303, forcing the movable spiral body 302 to deflect, so as to increase the included angle between the movable spiral body 302 and the fixed spiral body 301, thereby improving the mixing uniformity of the gas flowing between the movable spiral body 302 and the fixed spiral body 301.
[0044] When the pressure inside the premixing cavity 202 decreases, under the elastic recovery capacity of the elastic member 403, the movable part 401 drives the extrusion part 402 to move upward. When the extrusion part 402 moves upward, the pressing block on the extrusion part 402 is extruded with the rotating groove 304 on the rotating cylinder 303, forcing the movable spiral body 302 to deflect in the opposite direction, so as to reduce the included angle between the movable spiral body 302 and the fixed spiral body 301, thereby improving the flow rate of the gas flowing between the movable spiral body 302 and the fixed spiral body 301.
[0045] In the application process of the embodiment, when the mixing degree of the gas required by the cells inside the cell incubator is not high (such as a conventional immortalized cell line), the controller 9 controls the regulating valve at the communication hole 204 to be in a partially open state. At this time, the carbon dioxide and oxygen entering the premixing cavity 202 form a certain pressure, which pushes the movable part 401 to move downward. The movable part 401 drives the movable spiral body 302 to deflect through the extrusion part 402, and finally makes the included angle between the movable spiral body 302 and the fixed spiral body 301 be between 0° and 30°. After the carbon dioxide and oxygen are preliminarily mixed in the premixing cavity 202, they enter the first mixing cavity 2031 through the communication hole 204. Since the included angle between the movable spiral body 302 and the fixed spiral body 301 is between 0° and 30° at this time, after the gas enters the first mixing cavity 2031, although the gas will be partially mixed at the junction of the movable spiral body 302 and the fixed spiral body 301, since the included angle between the movable spiral body 302 and the fixed spiral body 301 is not large, the number of times of partial mixing of the gas will not be too much, that is, the gas flow will not be disturbed too much, so that the high flowability of the gas can be maintained to a certain extent.
[0046] After the gas is mixed in the first mixing cavity 2031, it enters the second mixing cavity 2032 through the through hole 2033. At this time, the concentration sensor inside the through hole 2033 detects the concentration of the mixed gas passing through the through hole 2033.
[0047] When the concentration sensor detects that the mixed gas concentration passing through the guide hole 2033 is in the set range, it indicates that the gas has been sufficiently mixed in the first mixing chamber 2031, at this time the regulating valve in the communication hole 204 remains in the current state, at this time the mixed gas passes through the second mixing chamber 2032 after mixing, and enters the heating module 8 through the gas outlet pipe 6.
[0048] When the concentration sensor detects that the mixed gas concentration passing through the guide hole 2033 is not in the set range, it indicates that the gas is poorly mixed in the first mixing chamber 2031, resulting in uneven mixing of carbon dioxide and oxygen, at this time the controller 9 controls the regulating valve in the communication hole 204 to act, the regulating valve reduces the opening of the communication hole 204, so that the flow from the premixing chamber 202 into the first mixing chamber 2031 is reduced, causing the gas pressure in the premixing chamber 202 to increase, the movable part 401 drives the extrusion part 402 to gradually move down, the extrusion part 402 drives the movable screw body 302 to further deflect through the pressure block and the rotating cylinder 303, so that the included angle between the fixed screw body 301 and the movable screw body 302 is enlarged (the included angle is controlled between 50°-90°), thereby causing the number of gas cutting between the fixed screw body 301 and the movable screw body 302 to increase, through more intense radial mixing and reverse rotation, the mixing effect of the gas in the mixing device 2 is improved.
[0049] It should be noted that the extrusion part 402 is symmetrically distributed on the upper surface of the movable part 401, and the two extrusion parts 402 are respectively in transmission connection with the rotating cylinders 303 in the two mixing chambers, so that when the movable part 401 drives the extrusion part 402 to move down, the movable screw body 302 in the first mixing chamber 2031 and the second mixing chamber 2032 deflects synchronously, so that the included angle between the fixed screw body 301 and the movable screw body 302 is enlarged, so as to improve the mixing effect of the gas in the mixing device 2.
[0050] When the cell culture box inside the cell has a higher requirement for the mixing degree of the gas (such as embryonic stem cells), the controller 9 controls the regulating valve to further reduce the opening size of the communication hole 204, at this time the carbon dioxide and oxygen entering the premixing chamber 202 will be compressed by a certain amount before entering the first mixing chamber 2031 from the communication hole 204, when the carbon dioxide and oxygen are compressed in the premixing chamber 202, the gas pressure drives the movable part 401 to move down, the movable part 401 drives the movable screw body 302 to deflect through the extrusion part 402, so that the included angle between the movable screw body 302 and the fixed screw body 301 is enlarged (the included angle is controlled between 80°-90°), causing the number of gas cutting between the fixed screw body 301 and the movable screw body 302 to increase, through more intense radial mixing and reverse rotation, the mixing effect of the gas in the mixing device 2 is improved. With the increase of the number of cutting, the gas resistance increases, the friction coefficient rises, and the flowability of the gas decreases to meet the requirements of high-precision concentration.
[0051] After the gas is mixed in the first mixing chamber 2031, it enters the second mixing chamber 2032 through the through hole 2033. At this time, the concentration sensor inside the through hole 2033 detects the concentration of the mixed gas passing through the through hole 2033.
[0052] When the concentration sensor detects that the concentration of the mixed gas passing through the through hole 2033 is within the set range, it indicates that the gas has been sufficiently mixed in the first mixing chamber 2031. At this time, the regulating valve in the communication hole 204 remains in the current state. At this time, after the mixed gas is mixed in the second mixing chamber 2032, it enters the heating module 8 through the gas outlet pipe 6.
[0053] When the concentration sensor detects that the concentration of the mixed gas passing through the through hole 2033 is not within the set range, it indicates that the mixing effect of the gas in the first mixing chamber 2031 is poor, resulting in uneven mixing of carbon dioxide and oxygen. At this time, the controller 9 controls the regulating valve in the communication hole 204 to act, and the regulating valve continuously expands and shrinks the opening of the communication hole 204.
[0054] When the regulating valve expands the opening of the communication hole 204, the flow from the premixing chamber 202 into the first mixing chamber 2031 is expanded. At this time, the movable part 401 drives the extrusion part 402 to gradually move up under the elastic recovery ability of the elastic part 403. The extrusion part 402 drives the movable screw body 302 to reverse deflection through the pressure block and the rotating cylinder 303. When the regulating valve shrinks the opening of the communication hole 204, the flow from the premixing chamber 202 into the first mixing chamber 2031 is further reduced, and the gas pressure in the premixing chamber 202 increases. The movable part 401 drives the extrusion part 402 to move down, and the extrusion part 402 drives the movable screw body 302 to positively deflect through the pressure block and the rotating cylinder 303.
[0055] When the regulating valve continuously expands and shrinks the opening of the communication hole 204, the movable screw body 302 in the first mixing chamber 2031 and the second mixing chamber 2032 continuously reverses, that is, the screw assembly 3 is converted from a static mixing state to a dynamic mixing state. The movable screw body 302 in positive and reverse rotation continuously disturbs the gas in different directions, so that the gas entering the first mixing chamber 2031 and the second mixing chamber 2032 is more fully mixed to meet the high-precision requirement of gas concentration.
[0056] It should be noted that: because the pitch of the spiral groove 304 located in the first mixing cavity 2031 is greater than the pitch of the spiral groove 304 located in the second mixing cavity 2032, when the opening of the communication hole 204 is continuously expanded and reduced by the adjusting valve, the rotation rate of the movable screw body 302 located in the first mixing cavity 2031 is less than the rotation rate of the movable screw body 302 located in the second mixing cavity 2032, so that the mixed gas entering the second mixing cavity 2032 can be more uniformly mixed to meet the high precision concentration requirement, and avoid the mixed gas entering the second mixing cavity 2032 from being mixed unevenly, and the general rotation rate cannot form sufficient disturbance, resulting in that the mixed gas entering the cell incubator is still in the phenomenon of uneven mixing.
[0057] It should be noted that: in the embodiment, when the movable part 401 moves from the middle area to the bottom area of the premixing cavity 202, the pressing block on the extrusion part 402 moves from the top to the bottom of the spiral groove 304, and when the pressing block moves from the top to the bottom of the spiral groove 304, the rotation number of the movable screw body 302 is greater than one turn, and the rotation number of the movable screw body 302 is adjusted by setting the pitch and number of turns of the spiral groove 304. By controlling the position of the movable part 401 in the premixing cavity 202, the included angle between the movable screw body 302 and the fixed screw body 301 is controlled.
[0058] Embodiment three Although the cell incubator gas supply device designed in the above embodiment can meet the precision requirement of different cells for gas mixing concentration to a certain extent, however, in the long-term actual application process, the heating module and the mixing device in the gas supply device lack monitoring mechanism for gas concentration and gas temperature, and an effective concentration and temperature compensation system cannot be constructed. In view of this, the technical improvement is carried out on the basis of embodiment two, and the improved technical scheme is as follows: The present application provides a gas concentration and temperature compensation method based on cell culture: Step one, data acquisition: collect gas concentration and temperature data through the concentration acquisition unit and the temperature acquisition unit.
[0059] The concentration acquisition unit includes a concentration sensor located inside the lead-through hole 2033 for detecting the concentration of the mixed gas passing through the lead-through hole 2033.
[0060] The temperature acquisition unit includes a temperature measuring element 803 (temperature sensor) arranged inside the heat conduction cavity 802 for real-time temperature measurement of the mixed gas in the heat conduction cavity 802.
[0061] By setting appropriate sampling frequency for the temperature acquisition unit and the concentration acquisition unit, the gas concentration and temperature data are continuously collected. For example, data is collected once every 1-5 minutes to capture the dynamic changes of environmental parameters.
[0062] Step 2: Model building: Construct a mathematical model of the gas concentration and temperature changes in the cell culture environment, and establish the temperature and gas concentration change curves.
[0063] Integrate the core physical properties of the culture container (material thermal conductivity, geometric dimensions, ventilation efficiency) and real-time environmental parameters (CO2 concentration gradient, temperature distribution) to establish a dynamic environmental database.
[0064] Based on the construction of a dynamic environment database, a machine learning algorithm is used for modeling. This embodiment uses the long short-term memory network (LSTM) in the neural network algorithm for time series modeling, and combines algorithms such as support vector machine (SVM) to train a multimodal experience model. The model adopts a layered architecture: Input layer: Integrates container parameters and real-time sensor data, where the sensor data covers key indicators such as gas concentration and temperature.
[0065] Hidden layer: Through deep mining, the nonlinear mapping relationship between environmental parameters and cell growth rate, survival rate, and differentiation state is revealed. This process refers to the correlation between single-cell transcriptome data and metabolites to enhance the biological plausibility of the model.
[0066] Output layer: Based on the input data and the analysis results of the hidden layer, it generates a dynamic environmental control curve for specific cell types, providing a scientific basis for the precise control of the cell culture environment.
[0067] To facilitate user operation and data interpretation, this embodiment is provided with a display screen electrically connected to the controller 9 on the housing 1 to realize interactive visualization function. The content displayed on the display screen mainly includes the following two aspects: Customized environmental curve display: Dynamically displays temperature-CO2 concentration synergistic change curves based on user-selected cell types, such as human stem cells and hypoxia-tolerant cells. For example, during the stem cell maturation cycle, a CO2 pulse regulation strategy is adopted and intuitively displayed through a visual interface.
[0068] Growth Status Prediction Dashboard: This dashboard maps in real time the impact of environmental parameter fluctuations on cell morphology (e.g., pseudopodia formation) and metabolic activity (ATP production rate). This visual dashboard allows users to intuitively understand the correlation between environmental parameter changes and cell phenotype, providing a reference for optimizing cell culture processes.
[0069] Step 3: Algorithm design: Based on the established model, design a compensation algorithm for gas concentration and temperature.
[0070] This embodiment combines the actual needs of biological culture equipment and uses the classic PID control algorithm to design the gas concentration and temperature compensation system. When the gas concentration or temperature deviates from the set value, the algorithm calculates the amount of adjustment needed. For example, if the temperature is lower than the set value, the algorithm will calculate the amount of heat the heating device needs to provide based on the temperature drop and model prediction.
[0071] The PID control algorithm system is specifically described as follows: Gas concentration compensation design principle: Dynamic proportional adjustment (P section): In terms of gas concentration compensation, the system uses a dynamic proportional adjustment mechanism.
[0072] When the sensor detects that the target gas concentration (such as CO2) is lower than the set value, the system rapidly increases the electromagnetic valve opening according to the proportion of the deviation to quickly supplement the gas. For example, when the CO2 concentration drops by 5%, the valve opening will be proportionally increased accordingly, achieving instantaneous response.
[0073] Integral elimination of steady-state error (I section): For long-term concentration drift problems caused by environmental temperature fluctuations (such as diurnal temperature difference leading to changes in CO2 solubility), the integral term continuously accumulates small deviations.
[0074] When the accumulated deviation exceeds the preset threshold, the system automatically fine-tunes the gas supply to eliminate the concentration deviation after a long period of operation, ensuring that the concentration is maintained within the set range (such as 5% CO2 ± 0.2%).
[0075] Derivative suppresses sudden disturbances (D section): When external disturbances occur (such as opening the incubator door causing a sudden change in airflow), the derivative term adjusts in advance according to the rate of change in concentration. For example, when the CO2 concentration drops by 2% within 1 second, the system can predict the downward trend and increase the gas supply in advance, effectively suppressing concentration oscillation.
[0076] Multi-gas collaborative control: The system uses a cascade PID structure for multi-gas collaborative control.
[0077] The main PID calculates the total ratio of O2 / CO2 based on the target concentration, and the secondary PID controls the opening of the double-channel electromagnetic valve to ensure the accuracy of the mixed gas ratio.
[0078] Temperature compensation design principle: The system uses a zoning and weighting control strategy to divide the culture area into a core culture zone, an edge buffer zone, and a gas inlet preheating zone, and assigns different weights and control objectives to each zone.
[0079] The core culture zone (weight 60%) prioritizes maintaining 37°C ± 0.1°C to quickly respond to temperature fluctuations; Edge buffer (weight 30%) allows 36.8℃±0.3℃ to avoid excessive energy consumption; Intake preheating band (weight 10%) sets 38℃±0.5℃ to compensate for heat loss when gas flows in.
[0080] At the same time, the system monitors the ambient temperature through auxiliary temperature sensors, and when it detects changes in the ambient temperature (such as when the laboratory air conditioner starts and stops), it adjusts the thermoelectric potential readings in real time. For example, when the environment warms up by 2℃, the software will automatically increase the reading by 0.5℃ to offset the measurement error.
[0081] When the temperature deviation exceeds 1℃ (such as abnormal heating caused by heating module failure), the system will suspend the integral term and only enable proportional and differential control to avoid continuous heating causing cell damage. At the same time, the system will trigger an alarm and cut off the heat source to ensure safety.
[0082] It should be noted that the PID control system in this embodiment adjusts adaptively according to the cell growth stage. During the stem cell differentiation period, the system increases the proportional coefficient (P) and the differential coefficient (D) to quickly respond to temperature fluctuations caused by metabolic heat; during the cell maturation period, the system enhances the integral coefficient (I) to maintain long-term temperature stability.
[0083] At the same time, the system embeds a periodic disturbance algorithm to fluctuate the CO2 concentration (±0.5%) and temperature (±0.3℃) in a 24-hour cycle to simulate the human circadian rhythm and promote physiological maturation of stem cells.
[0084] Step four, execution control: according to the results calculated by the algorithm, control the gas supply system to make corresponding adjustments.
[0085] Step five, monitoring and optimization: continuously monitor the gas concentration, temperature and cell growth state, and optimize and adjust the algorithm.
[0086] Evaluate cell growth by observing cell morphology under a microscope, detecting cell metabolites through biochemical analysis, and other methods. If the cell growth state is found to be poor, analyze whether it is caused by inaccurate gas concentration or temperature control, and adjust the parameters of the algorithm to improve the accuracy and stability of control.
[0087] It should be noted that: Finally, it should be noted that the above only describes the preferred embodiments of the present application and is not intended to limit the present application. Although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent replacements to some technical features, as long as they are within the spirit and principles of the present application. Any modification, equivalent replacement, improvement, etc. made within the scope of the present application should be included in the protection scope of the present application.
[0088] While embodiments of the application have been shown and described, it is to be understood that the application is not limited to the details of the embodiments described, since numerous changes, modifications, substitutions and alterations can be made thereto without departing from the spirit and scope of the application as defined by the appended claims and their equivalents.
Claims
1. A carbon dioxide gas supply device for cell culture comprising a housing, characterized by, The shell is provided with a mixing device, gas enters the mixing device through the air inlet pipe, the mixed gas enters the heating module through the air outlet pipe, and the mixed gas enters the cell incubator after being heated by the heating module; The inside of the mixing device is symmetrically provided with a spiral assembly, which includes fixed spirals and movable spirals arranged alternately, the fixed spirals are fixedly connected with the mixing device, and the movable spirals are rotatably connected with the fixed spirals; The lower part of the spiral assembly is provided with a pressure receiving assembly which is in transmission connection with the movable spirals, by adjusting the pressure receiving degree of the pressure receiving assembly, the included angle between the movable spirals and the fixed spirals is changed to adapt to the gas supply requirements of different cells.
2. The carbon dioxide gas supply apparatus for cell culture according to claim 1, wherein The mixing device comprises: a body fixedly arranged in the inside of the shell; a premixing cavity located at the bottom region of the body, and the pressure receiving assembly is located in the inside of the premixing cavity; a mixing part located above the premixing cavity, and the spiral assembly is located in the inside of the mixing part; a communication hole arranged at the junction of the premixing cavity and the mixing part, and an adjusting member is arranged on the communication hole to adjust the flow rate of the gas entering the mixing part through the communication hole.
3. The carbon dioxide gas supply apparatus for cell culture according to claim 2, wherein The mixing part comprises: a first mixing cavity and a second mixing cavity, which are symmetrically arranged above the premixing cavity, and each of which is provided with a spiral assembly in the inside; a through hole, the first mixing cavity and the second mixing cavity are in communication with each other through the through hole, and a gas concentration detection unit is arranged in the inside of the through hole.
4. The carbon dioxide gas supply apparatus for cell culture according to claim 3, wherein The movable spirals are rotatably connected with the fixed spirals through a rotating cylinder, a rotating groove is arranged on the rotating cylinder, and the rotating cylinder is in transmission connection with the pressure receiving assembly through the rotating groove.
5. The carbon dioxide gas supply apparatus for cell culture according to claim 4, wherein The pressure receiving assembly comprises: a movable part arranged in the inside of the premixing cavity and in sliding connection with the premixing cavity; a pressing part arranged at the top of the movable part, one end of the pressing part located in the rotating cylinder is provided with a pressing block, and the pressing block is in contact with the rotating groove; a resilient member arranged at the bottom of the movable part to buffer the pressure received by the pressing part.
6. The carbon dioxide gas supply apparatus for cell culture according to claim 5, wherein The pitch of the rotating groove in the first mixing cavity is greater than the pitch of the rotating groove in the second mixing cavity.
7. The carbon dioxide gas supply apparatus for cell culture according to claim 1, wherein The heating module comprises: a heating seat connected with the air outlet pipe, and a heat conducting cavity for heating the mixed gas is arranged in the inside of the heating seat; a heating unit arranged in the heating seat to provide heat for the heat conducting cavity; a temperature measuring element arranged in the inside of the heat conducting cavity to detect the temperature change of the mixed gas when heated; an air outlet arranged on the outside of the heating seat and in communication with the heat conducting cavity, and the mixed gas after being heated enters the inside of the cell incubator through the air outlet.
8. The carbon dioxide gas supply apparatus for cell culture according to claim 7, wherein A filter is arranged on the air outlet pipe to filter impurities in the mixed gas.
9. The carbon dioxide gas supply apparatus for cell culture according to claim 2, wherein The outlet end of the air inlet pipe enters the premixing cavity through a proportional valve, and the gas is preliminarily mixed in the inside of the premixing cavity.
10. The carbon dioxide gas supply apparatus for cell culture according to claim 7, wherein A controller is arranged in the inside of the shell, and all the electrical elements in the inside of the shell are in electrical connection with the controller.
Citation Information
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