An artificial intelligence cell culture monitoring method and system

By detecting cell activity and density in real time during cell culture and adjusting the parameters of smart stirrer and oscillator, the cell damage caused by the failure of smart devices to be adjusted in time is solved, and precise control and optimization of cell culture is achieved.

CN120005720BActive Publication Date: 2025-08-08SHENZHEN WINGOR BIO TECH
View PDF 4 Cites 0 Cited by

Patent Information

Application Number
CN202510498132.X
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-04-21
Publication Date
2025-08-08
Estimated Expiration
2045-04-21

AI Technical Summary

Technical Problem

In the prior art, smart devices fail to adapt in time during cell culture, resulting in cell damage.

Method used

By performing cell activity detection in the bioreactor, cell density and clump impact values are obtained, whether to perform review adjustments, and the parameters of the smart stirrer and oscillator are adjusted according to the cell status, precise control and personalized optimization of the cell culture process are achieved.

Benefits of technology

Accurate control and personalized optimization of the cell culture process are achieved, cell damage is avoided, and the stability and success rate of cell culture are improved.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN120005720B_ABST
    Figure CN120005720B_ABST
Patent Text Reader

Abstract

The present invention discloses an artificial intelligence cell culture monitoring method and system, which belongs to the field of electrical digital data processing technology, and includes the following steps: S1, performing cell activity detection based on initial cells in a bioreactor, thereby judging whether to perform intelligent auxiliary adjustment; S2, obtaining a preset stirring speed and a culture limit parameter set; S3, obtaining a cell agglomerate impact value; S4, judging whether to perform review adjustment based on cell density and cell agglomerate impact value analysis; if the review adjustment is not performed, sending an intelligent auxiliary adjustment end signal to the intelligent terminal; if the review adjustment is performed, obtaining an auxiliary adjustment judgment result, and adjusting the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator according to the settings; S5, obtaining a cell review status value, thereby adjusting the intelligent stirrer accordingly, solving the problem of cell damage caused by the failure of intelligent equipment to perform adaptive adjustment in a timely manner during the cell culture process in the prior art.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] The present invention relates to the technical field of electrical digital data processing, and in particular to an artificial intelligence cell culture monitoring method and system. Background Art

[0002] With the widespread increase in demand for cell culture, artificial intelligence technology has been widely used in the cell culture monitoring process. Existing cell culture monitoring methods optimize algorithms by analyzing the noise interference or system errors of the equipment to achieve cell number monitoring. However, they ignore the problem of cell damage caused by the failure of intelligent equipment to make timely adaptive adjustments during the cell culture process.

[0003] For example, the invention patent with publication number CN117421691B discloses an AI-based cell culture monitoring method and system, which includes data acquisition, data preprocessing, impedance prediction, cell volume concentration calculation, initial parameter search, and cell culture monitoring. The raw data is preprocessed to minimize noise and system errors, and key parameters are extracted from the impedance signal using a hybrid equivalent circuit model, which is then used to determine the cell volume concentration. The inertia weight parameter is adjusted based on the current optimal and worst fitness values, balancing the relationship between parameter positions in global and local searches. The parameter position is updated based on the individual empirical optimal and global optimal values, and the search results are judged based on the fitness threshold and the maximum number of iterations.

[0004] For example, the invention patent with publication number CN117932382B discloses a novel environment-controllable cell culture method, which includes: collecting multiple monitoring data and interference data, and constructing an internal monitoring matrix and an interference matrix; identifying mutation points based on the internal monitoring matrix, and obtaining time response delay influencing factors according to the irrelevant factors of the mutation points in different rows; obtaining clusters according to the interference matrix, and clustering the internal monitoring matrix through the clusters of the interference matrix, and thereby constructing a window to obtain the main differential feedback coefficient; obtaining the differential hysteresis index according to the time response delay influencing factor and the main differential feedback coefficient; obtaining the adjustment strength of the environmental data according to the differential hysteresis index; completing the adjustment of the environmental data and completing the cell culture, thereby enhancing the efficiency of target control and enhancing the robustness and timeliness of the algorithm.

[0005] However, in the process of implementing the technical solutions of the invention in the embodiments of the present application, the present application found that the above technology has at least the following technical problems:

[0006] In the existing technology, cell number monitoring is achieved only by analyzing the noise interference or system errors of the equipment and optimizing the algorithm. However, it ignores the impact of the equipment parameters on cell activity during the cell culture process due to the inability to adjust the size of the equipment according to the cell status in a timely manner. Therefore, there is a problem of cell damage caused by the failure to make timely adaptive adjustments. Summary of the Invention

[0007] The embodiments of the present application provide an artificial intelligence cell culture monitoring method and system to solve the problem of cell damage caused by the failure of intelligent devices to make timely adaptive adjustments during the cell culture process in the prior art, thereby achieving precise control and personalized optimization of the cell culture process.

[0008] An embodiment of the present application provides an artificial intelligence cell culture monitoring method, comprising the following steps: S1. When the intelligent terminal receives a cell proliferation signal, it performs cell activity detection based on the initial cells in the bioreactor to determine whether to perform intelligent assisted adjustment; S2. If intelligent assisted adjustment is to be performed, the size parameters and cell activity density of the bioreactor are obtained, and the preset stirring speed and culture limit parameter set are obtained by analysis; S3. The intelligent agitator performs stirring based on the preset stirring speed, and obtains the cell density and cell state parameters according to the preset sampling interval, and analyzes to obtain the cell agglomerate influence value; S4. Based on the analysis of the cell density and cell agglomerate influence value, it is determined whether to perform review adjustment. If review adjustment is not to be performed, an intelligent assisted adjustment end signal is sent to the intelligent terminal. If review adjustment is to be performed, an assisted adjustment determination result is obtained, and the stirring speed of the intelligent agitator and the equipment parameters of the intelligent oscillator are adjusted according to the settings; S5. The cell review state parameters are obtained, and the cell review state values are analyzed to obtain the cell review state values, thereby adjusting the intelligent agitator accordingly.

[0009] An embodiment of the present application provides an artificial intelligence cell culture monitoring system, comprising: a cell culture judgment module, an initial culture module, an intelligent stirring execution module, a review and adjustment judgment module, and a stirring adjustment module; wherein the cell culture judgment module is configured to, upon receiving a cell proliferation signal from an intelligent terminal, perform cell activity detection based on initial cells in a bioreactor, thereby determining whether to perform intelligent assisted adjustment; the initial culture module is configured to, if intelligent assisted adjustment is to be performed, obtain dimensional parameters and cell activity density of the bioreactor, and analyze to obtain a preset stirring speed and a set of culture-limited parameters; the intelligent stirring execution module is configured to cause an intelligent stirrer to perform stirring at a preset stirring speed, and to obtain cell density and cell state parameters at a preset sampling interval, and analyze to obtain a cell clumping impact value; the review and adjustment judgment module is configured to determine whether to perform review and adjustment based on the cell density and cell clumping impact value; if review and adjustment is not to be performed, an intelligent assisted adjustment end signal is sent to the intelligent terminal; if review and adjustment is to be performed, an assisted adjustment judgment result is obtained, and the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator are adjusted accordingly. The stirring adjustment module is used to obtain the cell review state parameters, analyze and obtain the cell review state value, and adjust the intelligent stirrer accordingly.

[0010] One or more technical solutions provided in the embodiments of this application have at least the following technical effects or advantages:

[0011] 1. The present invention provides an artificial intelligence cell culture monitoring method. By detecting the cell activity of the initial cells in the bioreactor, it determines whether to perform intelligent-assisted adjustment. When performing intelligent-assisted adjustment, the dimensional parameters and cell activity density of the bioreactor are obtained, and the preset stirring speed and culture limit parameter set are analyzed to determine the appropriate stirring speed and culture parameters. This achieves precise control and personalized optimization of the cell culture process, effectively solving the problem of cell damage caused by the failure of intelligent devices to make timely adaptive adjustments during the cell culture process in the existing technology.

[0012] 2. The present invention determines whether to perform review and adjustment based on the analysis of cell density and cell agglomeration impact value. If review and adjustment is performed, an auxiliary adjustment determination result is obtained, and the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator are adjusted accordingly. The equipment parameters are adjusted in time according to the changes in cell density and cell agglomeration impact value, thereby realizing dynamic monitoring and optimization of the cell culture process, ensuring that the cells are always in the best growth environment.

[0013] 3. The present invention obtains cell review status parameters and analyzes the cell review status values, thereby adjusting the intelligent agitator accordingly, thereby further optimizing and adjusting the equipment according to the cell review status parameters, thereby realizing multi-stage, all-round monitoring and regulation of the cell culture process, and improving the stability and success rate of cell culture.

[0014] 4. The present invention obtains the shear force in the cell culture process in real time after adjusting the stirring speed of the intelligent stirrer, thereby determining whether to adjust the equipment parameters in real time, and controlling the equipment parameters to not be lower than the lower limit of the culture limit parameter set during the adjustment process, thereby effectively protecting the cells from damage caused by excessive shear force, and avoiding excessive adjustment that causes the cells to be unable to fully disperse, thereby achieving refined protection and regulation of the cell culture process, and effectively solving the problem of cell mechanical damage caused by untimely shear force monitoring and equipment parameter adjustment in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 A flow chart of an artificial intelligence cell culture monitoring method provided in an embodiment of the present application;

[0016] Figure 2 A schematic diagram of the structure of an artificial intelligence cell culture monitoring system provided in an embodiment of the present application. DETAILED DESCRIPTION

[0017] The embodiments of the present application provide an artificial intelligence-based cell culture monitoring method and system, which solves the problem of cell damage caused by the failure of intelligent devices to make timely adaptive adjustments during the cell culture process in the prior art, thereby achieving precise control and personalized optimization of the cell culture process.

[0018] In order to better understand the above technical solution, the above technical solution will be described in detail below with reference to the accompanying drawings and specific implementation methods.

[0019] like Figure 1 As shown, it is a flow chart of an artificial intelligence cell culture monitoring method provided by an embodiment of the present application, which includes the following steps: S1. When the intelligent terminal receives a cell proliferation signal, it performs cell activity detection based on the initial cells in the bioreactor to determine whether to perform intelligent assisted adjustment; S2. If intelligent assisted adjustment is performed, the size parameters and cell activity density of the bioreactor are obtained, and the preset stirring speed and culture limit parameter set are obtained by analysis; S3. The intelligent stirrer performs stirring based on the preset stirring speed, and obtains the cell density and cell state parameters according to the preset sampling interval, and analyzes to obtain the cell agglomerate influence value; S4. Based on the cell density and cell agglomerate influence value, it is determined whether to perform review adjustment. If review adjustment is not performed, an intelligent assisted adjustment end signal is sent to the intelligent terminal. If review adjustment is performed, an assisted adjustment judgment result is obtained, and the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator are adjusted according to the settings; S5. The cell review state parameters are obtained, and the cell review state value is obtained by analysis, thereby adjusting the intelligent stirrer accordingly.

[0020] In this embodiment, it should be noted that during the stirring process, the cells can exchange substances with organic matter in the culture medium, thereby allowing the cells to grow and proliferate in the culture medium, thereby continuously increasing the cell density. If the cell number decreases during the cell activity test or fails to reach the preset termination cell density, it indicates that the cell activity is poor, and an early warning is issued.

[0021] It should be noted that the cell density and cell state parameters are obtained and analyzed to obtain the cell cluster influence value. The specific steps include: obtaining the cell state parameters, which include the size of each cell cluster, the number of cell clusters and the proportion of oversized cell clusters; obtaining the preset cell cluster allowable set in the database, performing a difference analysis between the cell density and the cell density reference value, performing a difference analysis between the size of each cell cluster and the cell cluster size reference value, and then introducing the corresponding influencing factors, and fusing the proportion of oversized cell clusters with the influencing factor of the unit oversized cell cluster ratio, and fusing the number of cell clusters with the influencing factor of the unit cell cluster number to obtain the cell cluster influence value.

[0022] The cell cluster influence value is obtained by comparing it with the cell density and cell state parameters; the cell cluster allowable set includes the cell density reference value, the cell cluster size reference value, the influencing factor of the number of cell clusters per unit, and the influencing factor of the proportion of oversized cell clusters per unit.

[0023] All parameters in this application have been de-unitized, that is, all data have been de-unitized.

[0024] The size of individual cell aggregates, the number of cell aggregates, and the proportion of oversized cell aggregates can be measured using the LUNA-FX7 cell counter. Cell density can be measured using online cell density sensors (such as Incyte and Dencytee).

[0025] The cell mass impact value is obtained by:

[0026] ;

[0027] Where, represents the cell mass impact value, represents the cell density, represents the reference value of cell density, represents the size of the i-th cell cluster, i represents the number of the cell cluster, , represents the total number of cell aggregates, represents the reference value of cell aggregate size, Indicates the number of cell clumps, represents the factor affecting the number of unit cell clusters, Indicates the proportion of oversized cell clusters, Indicates the influencing factor of the proportion of oversized cell clusters per unit, represents the cell density influencing factor, represents the factor affecting the size of cell aggregates.

[0028] It should be noted that oversized cell aggregates refer to cell aggregates that are larger than the preset size in the database.

[0029] It should also be noted that the unit cell cluster number influencing factor and the unit over-specification cell cluster ratio influencing factor can be obtained from the database. For example, the unit cell cluster number influencing factor can be obtained by obtaining the historical cell cluster number stored in the database and the unit cell cluster number influencing factor corresponding to the historical cell cluster number, and constructing a cell cluster number influencing factor mapping set. The unit cell cluster number influencing factor can be obtained by inputting the real-time cell cluster number into the cell cluster number influencing factor mapping set. The method for obtaining the unit over-specification cell cluster ratio influencing factor is the same as the method for obtaining the unit cell cluster number influencing factor, and both can be obtained through obtaining them in the mapping set, where the unit over-specification cell cluster ratio influencing factor corresponds to the over-specification cell cluster ratio mapping set.

[0030] It should be noted that the cell density influencing factor can be obtained by obtaining the historical cell density stored in the database, and the cell density influencing factor corresponding to the historical cell density, thereby constructing a cell density mapping set, wherein there is a one-to-one or many-to-one correspondence in the mapping set. The cell density influencing factor can be obtained by inputting the cell density data to be used into the cell density mapping set. The method for obtaining the cell cluster size influencing factor is the same as the method for obtaining the cell density influencing factor, and can also be matched in the corresponding mapping set, wherein the cell cluster size influencing factor corresponds to the cell cluster size mapping set.

[0031] By analyzing the cell density and cell state parameters, the cell clumping impact value is obtained, which takes into account the mutual influence relationship between these parameters. For example, the higher the cell density, the more cells have undergone cell proliferation and the better the cell state. If there are more cell clumpings, it will affect the full contact between the cells and the culture medium, resulting in the cells being unable to fully obtain nutrients, affecting cell proliferation, and then affecting the cell density. The more cell clumpings and the larger the cell clumpings, the more difficult it is for the cells to absorb organic matter for growth and proliferation, and therefore the more serious the impact on cell culture.

[0032] Furthermore, cell activity detection is performed based on the initial cells in the bioreactor to determine whether to perform intelligent assisted adjustment. The specific steps include: pre-stirring the cells at a set pre-stirring speed based on the initial cells in the bioreactor, obtaining the cell density after the pre-stirring is completed, and marking it as the cell activity density; obtaining the initial cell density in the bioreactor, and performing difference processing with the cell activity density to obtain the culture difference, and comparing it with the preset termination cell density in the database. If the culture difference is above the termination cell density, intelligent assisted adjustment is performed. If the culture difference is less than the termination cell density, intelligent assisted adjustment is not performed, and an early warning reminder is issued.

[0033] In this embodiment, it should be noted that the final cell density preset in the database refers to the cell density that needs to be increased after the initial cells in the bioreactor are pre-mixed.

[0034] By testing the cell density after pre-stirring (labeled as "cell activity density") and analyzing it, if the cell activity density is greater than the lower limit of cell density, cell culture will be carried out. If the cell activity density is below the lower limit of cell density, cell culture will not be carried out and an early warning reminder will be issued. This can avoid interference with the subsequent adjustment of stirring parameters due to poor cell activity and also avoid unnecessary cell culture. If the cell activity itself is poor, more gentle operation is required during cell stirring and cell shaking to prevent shear damage caused by incorrectly increasing the stirring speed due to low initial cell concentration, which further affects cell activity and affects cell culture.

[0035] It should be noted that the initial cell density in the bioreactor is obtained and subtracted from the cell activity density to obtain the culture difference. The culture difference may be a negative value. Here, the initial cell density should be subtracted from the cell activity density.

[0036] Furthermore, the size parameters and cell activity density of the bioreactor are obtained, and the preset stirring speed and culture limit parameter set are obtained by analysis. The specific steps include: obtaining the size parameters of the bioreactor, which include the diameter of the bioreactor and the diameter of the stirring blade; obtaining the data reference set preset in the data, and performing a difference analysis with the size parameters of the bioreactor and the cell activity density to obtain the culture reference value; matching based on the culture reference value to obtain the preset stirring speed; the data reference set includes the ideal cell activity density, the unit bioreactor diameter influencing factor and the unit stirring blade diameter influencing factor; the culture reference value is to evaluate the degree of coupling between the diameter of the bioreactor and the stirring blade diameter and the unit bioreactor diameter influencing factor and the unit stirring blade diameter influencing factor respectively, and after coupling with the degree of difference between the cell activity density and the ideal cell activity density, the corresponding influence weight is introduced to obtain the culture reference value.

[0037] In this embodiment, it should be noted that the preset stirring speed is obtained by matching based on the culture reference value. The specific method is: obtain each culture reference value interval preset in the database and the reference initial stirring speed corresponding to each culture reference value interval, and match them with the culture reference value. If the culture reference value is within a preset culture reference value interval, the reference initial stirring speed corresponding to the interval is obtained as the preset stirring speed.

[0038] By obtaining the hardware parameters of the bioreactor diameter and the stirring blade diameter, combined with the cell activity density, and performing a difference analysis with the preset data reference set, the culture reference value is obtained, which indicates the degree of deviation between the actual hardware configuration and cell activity density and the ideal state. The preset stirring speed and culture limit parameter set are then matched to ensure that the preset stirring speed accurately matches the current reactor physical conditions and cell density conditions.

[0039] The diameter of the bioreactor and the diameter of the agitator blade can be obtained by querying the bioreactor equipment parameters. The cell activity density can be measured using an online cell density sensor (such as Incyte and Dencytee).

[0040] Culture reference values are derived by analyzing the bioreactor diameter, impeller diameter, and center-to-center spacing of the impellers, as well as the cell viability density. This takes into account the interplay between these parameters. For example, the bioreactor diameter determines the impeller diameter and stirring speed. Larger reactor diameters require larger impeller diameters and higher stirring speeds to ensure adequate mixing of the liquid. A larger diameter increases the liquid flow path, which compromises mixing efficiency and requires a higher stirring speed to compensate. The impeller diameter directly affects stirring efficiency and liquid flow. A larger impeller diameter provides stronger stirring force, while the ratio of impeller diameter to bioreactor diameter influences liquid flow characteristics and mixing efficiency. A larger spacing provides a longer flow path, which helps improve mixing efficiency. The cell viability density reflects the number of cells per unit volume and directly influences the cell's demand for nutrients and oxygen, as well as the rate of metabolic waste production. Higher cell densities require stronger stirring to ensure adequate nutrient and oxygen supply to the cells and the timely removal of metabolic waste. Cell density also affects the viscosity and flow characteristics of the liquid, indirectly impacting stirring efficiency.

[0041] The specific method to obtain the culture reference value is as follows:

[0042] ;

[0043] Where, represents the culture reference value, represents the cell activity density, represents the ideal cell activity density, represents the diameter of the bioreactor, represents the factor affecting the unit bioreactor diameter, Indicates the diameter of the stirring blade, Indicates the influence factor of unit stirring blade diameter, Indicates the distance between the blade centers, Indicates the reference value of the blade center point spacing, represents the influence weight of cell activity density, Indicates the influence weight of the distance between the blade centers.

[0044] It should be noted that the cell activity density influence weight and the blade center point spacing influence weight can be obtained from the database. For example, the cell activity density influence weight can be obtained by obtaining the historical cell activity density stored in the database, and the cell activity density influence weight corresponding to the historical cell activity density, thereby constructing a cell activity density mapping set, wherein there is a one-to-one or many-to-one correspondence in the mapping set. The cell activity density influence weight can be obtained by inputting the cell activity density data to be used into the cell activity density mapping set. The method for obtaining the blade center point spacing influence weight is the same as the method for obtaining the cell activity density influence weight, and can also be matched in the corresponding mapping set, wherein the blade center point spacing influence weight corresponds to the blade center point spacing mapping set.

[0045] The unit bioreactor diameter influence factor and the unit stirring blade diameter influence factor can be obtained from the database. For example, the unit bioreactor diameter influence factor can be obtained by obtaining the historical bioreactor diameters stored in the database and the unit bioreactor diameter influence factors corresponding to the historical bioreactor diameters, and constructing a bioreactor diameter influence factor mapping set. The unit bioreactor diameter influence factor can be obtained by inputting the real-time bioreactor diameter into the bioreactor diameter influence factor mapping set. The method for obtaining the unit stirring blade diameter influence factor is the same as the method for obtaining the unit bioreactor diameter influence factor, and both can be obtained through the mapping set, where the unit stirring blade diameter influence factor corresponds to the stirring blade diameter mapping set.

[0046] Furthermore, based on the analysis of cell density and cell clump influence value, it is determined whether to perform review and adjustment. The specific steps include: obtaining the cell clump influence threshold and cell density reference value preset in the database; comparing the cell density based on the cell density reference value, and comparing the cell clump influence value based on the cell clump influence threshold value; if the cell density is greater than the cell density reference value, and at the same time the cell clump influence value is below the cell clump influence threshold, review and adjustment will not be performed; otherwise, review and adjustment will be performed.

[0047] In this example, by simultaneously considering both cell density and the cell clumping effect, and comparing them with corresponding reference values and thresholds, a more comprehensive and accurate assessment of the cell culture status is achieved, avoiding errors associated with single-parameter assessments and ensuring precise adjustments to the cell culture equipment. For example, relying solely on cell density would overlook the impact of cell clumping on culture outcomes, whereas incorporating the cell clumping effect more accurately reflects the actual cell growth environment and requirements.

[0048] Based on different comparison results, specific equipment adjustment judgment results are given. When the cell density is below the cell density reference value and the cell clump impact value is greater than the cell clump impact threshold, the stirring speed of the intelligent stirrer is increased and the intelligent oscillator is activated. This helps reduce collisions and shear forces between cells and prevent excessive cell clumps from affecting cell growth and proliferation. When the cell density is lower than the reference value but the cell clump impact value is less than the threshold, the stirring speed is not adjusted but the intelligent oscillator is activated. This can improve cell distribution and nutrient supply, provide a more suitable growth environment for cells, and promote healthy cell growth and proliferation. By analyzing multiple possible combinations of cell density and cell clump impact values and setting clear equipment adjustment strategies for each situation, corresponding and reasonable adjustment plans can be made when facing different cell culture conditions, avoiding blindness and arbitrariness in equipment adjustment and improving the reliability and stability of the entire cell culture process. Moreover, this method can dynamically determine whether the cell culture equipment needs to be adjusted based on changes in cell density and cell clumping impact values during the cell culture process, enabling the cell culture process to promptly respond to changes in cell growth status and flexibly optimize culture conditions, thereby better meeting the needs of cells at different growth stages and improving the success rate and efficiency of cell culture.

[0049] Furthermore, if a review adjustment is performed, an auxiliary adjustment judgment result is obtained, and the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator are adjusted according to the settings. The specific steps include: if a review adjustment is performed, the cell density is compared with the cell density based on the cell density reference value, and the cell agglomerate influence value is compared with the cell agglomerate influence value based on the cell agglomerate influence threshold value; if the cell density is below the cell density reference value, and at the same time the cell agglomerate influence value is greater than the cell agglomerate influence threshold value, the first auxiliary adjustment judgment result is obtained by analysis, and the first auxiliary adjustment judgment result is to increase the stirring speed of the intelligent stirrer and start the intelligent oscillator; if the cell density is within the cell density reference value, If the cell density is greater than the cell density reference value and the cell clump influence value is greater than the cell clump influence threshold, then the analysis obtains a second auxiliary adjustment determination result, which is to keep the stirring speed of the intelligent stirrer constant and start the intelligent oscillator; if the cell density is greater than the cell density reference value and the cell clump influence value is greater than the cell clump influence threshold, then the analysis obtains a third auxiliary adjustment determination result, which is to lower the stirring speed of the intelligent stirrer and start the intelligent oscillator; based on the auxiliary adjustment determination result and the cell clump influence value, the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator are adjusted according to the settings.

[0050] In this embodiment, it should be noted that the cell density is greater than the cell density reference value, which proves that the cells are fully proliferating and the cell activity is good at this time. However, the cell agglomerate influence value is greater than the cell agglomerate influence threshold, which proves that some cells are not evenly stirred. In this case, the intelligent oscillator should be started to assist the cells in dispersing. At this time, if the stirring speed of the intelligent stirrer is kept unchanged, the cells will be subjected to a greater shear force. Therefore, the stirring speed of the intelligent stirrer needs to be lowered to prevent the cell activity from decreasing due to excessive shear force.

[0051] By comparing the cell clump influence value with the preset interval, the stirring speed adjustment coefficient and the initial swing parameters of the intelligent oscillator required under the current cell culture state can be accurately determined. The interval matching-based method avoids the error caused by a single threshold judgment and ensures the accuracy of the adjustment of the cell culture equipment. For example, different cell clump influence value intervals correspond to different stirring adjustment strategies, which can more carefully reflect the actual growth needs of the cells. Corresponding stirring execution adjustment coefficients and initial swing parameters of the intelligent oscillator are set for different cell clump influence value intervals, providing a variety of adjustment strategies, which means that when faced with different cell culture states, the most appropriate adjustment scheme can be flexibly selected instead of a fixed adjustment method, thereby better adapting to various changes in the cell culture process.

[0052] Through clear interval division and corresponding parameter settings, a reasonable basis for equipment adjustment is ensured for various cell clump impact values, avoiding arbitrary and blind equipment adjustments and improving the reliability and stability of the cell culture process. At the same time, adjustments based on preset parameters in the database also ensure the scientific and effective adjustment strategy. It can also dynamically and precisely adjust the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator according to the real-time changes in the cell clump impact value, flexibly optimizing culture conditions to better meet the needs of cells at different growth stages and improve the success rate and efficiency of cell culture.

[0053] Furthermore, based on the auxiliary adjustment judgment result and the cell clump influence value, and according to the setting, the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator are adjusted. The specific steps include: performing difference processing based on the cell density reference value and the cell density to obtain the density difference, matching based on the density difference, and obtaining the stirring speed of the first preset intelligent stirrer and the equipment parameters of the first preset intelligent oscillator; performing difference processing based on the cell clump influence threshold and the cell clump influence value to obtain the cell clump difference, matching based on the cell clump difference, and obtaining the stirring speed of the second preset intelligent stirrer and the equipment parameters of the second preset intelligent oscillator; if the auxiliary adjustment judgment result is the first auxiliary adjustment judgment result, the stirring speed of the first preset intelligent stirrer is adjusted to The stirring speed of the set-adjusted intelligent stirrer is obtained by averaging the stirring speed of the first preset intelligent oscillator with the stirring speed of the second preset intelligent oscillator, and the equipment parameters of the intelligent oscillator are obtained by averaging the equipment parameters of the first preset intelligent oscillator with the equipment parameters of the second preset intelligent oscillator; if the auxiliary adjustment judgment result is the second auxiliary adjustment judgment result, the stirring speed preset in the database is obtained as the stirring speed of the preset-adjusted intelligent stirrer; if the auxiliary adjustment judgment result is the third auxiliary adjustment judgment result, the stirring speed of the second preset intelligent stirrer and the equipment parameters of the second preset intelligent oscillator are used as the stirring speed of the set-adjusted intelligent stirrer and the equipment parameters of the intelligent oscillator, and the equipment parameters of the intelligent oscillator include the swing amplitude and swing frequency of the intelligent oscillator.

[0054] In this embodiment, it should be noted that the number of reviewed cell clusters, the proportion of reviewed oversized cell clusters, and the reviewed average cell cluster size can be measured by a LUNA-FX7 cell counter.

[0055] By obtaining cell review status parameters (reviewed cell clump number, reviewed over-specification cell clump ratio, reviewed average cell clump size, and average change in cell clump size), and performing differential analysis on them compared with the preset cell clump review permission set in the database, the status of cell culture can be comprehensively and meticulously evaluated, avoiding the one-sidedness that may be caused by a single parameter evaluation and ensuring the accuracy of adjustments to cell culture equipment.

[0056] According to the changes in the cell review status parameters, the device parameters of the intelligent oscillator are dynamically adjusted, so that the cell culture process can respond to the changes in the cell growth status in a timely manner and flexibly optimize the culture conditions, thereby better meeting the needs of cells in different growth stages and improving the success rate and efficiency of cell culture.

[0057] Furthermore, the cell review status parameters are obtained, and the cell review status value is obtained by analysis, thereby adjusting the intelligent stirrer accordingly. The specific method is as follows: obtaining the cell review status parameters, which include the number of reviewed cell clusters, the proportion of reviewed over-specification cell clusters, and the average size of reviewed cell clusters; obtaining the preset cell cluster review permission set in the database, and performing differential analysis with the cell review status parameters to obtain the cell review status value; the cell cluster review permission set includes the unit review cell cluster number influencing factor, the unit review over-specification cell cluster proportion influencing factor, and the review cell cluster size reference value; the cell review status value is obtained by evaluating the coupling of the number of reviewed cell clusters and the proportion of reviewed over-specification cell clusters with the review cell cluster number influencing factor and the unit review over-specification cell cluster proportion influencing factor, respectively. The degree of combination is calculated, and the difference between the reviewed average cell cluster size and the reviewed cell cluster size reference value is combined, and then the corresponding influence weight is introduced to obtain the cell review status value; the review cell density is compared with the cell density reference value, and the cell review status value is compared with the cell review status threshold value; if the review cell density is greater than the cell density reference value, and at the same time the cell review status value is below the cell review status threshold value, an intelligent auxiliary adjustment end signal is sent to the intelligent terminal, otherwise the intelligent oscillator is adjusted; the intelligent oscillator is adjusted, and the specific method is to obtain the review cell density and combine it with the cell review status value analysis to obtain the device adjustment parameters of the intelligent oscillator, and adjust the swing amplitude of the intelligent oscillator upward based on the device adjustment parameters of the intelligent oscillator, and adjust the swing frequency of the intelligent oscillator upward.

[0058] In this embodiment, the cell review status value is obtained by:

[0059] ;

[0060] Where, Indicates the cell review status value, Indicates the number of reviewed cell clumps, represents the impact factor of the number of cell clusters per unit review, Indicates the review of the proportion of oversized cell clusters, Indicates the impact factor of the unit review of the proportion of oversized cell clusters, represents the reviewed average cell clump size, Indicates review of reference values for cell clump size.

[0061] It should be noted that the unit review cell cluster number influencing factor and the unit review over-specification cell cluster proportion influencing factor can be obtained from the database. For example, the unit review cell cluster number influencing factor can be obtained by obtaining the historical unit review cell cluster number stored in the database, and the unit review cell cluster number influencing factor corresponding to the historical unit review cell cluster number, thereby constructing a unit review cell cluster number mapping set, wherein there is a one-to-one or many-to-one correspondence in the mapping set. The unit review cell cluster number influencing factor can be obtained by inputting the unit review cell cluster number data to be used into the unit review cell cluster number mapping set. The method for obtaining the unit review over-specification cell cluster proportion influencing factor is the same as the method for obtaining the unit review cell cluster number influencing factor, and both can be matched in the corresponding mapping set, wherein the unit review over-specification cell cluster proportion influencing factor corresponds to the unit review over-specification cell cluster proportion mapping set.

[0062] By comparing the cell review status value with the preset cell density reference value, it is possible to accurately determine whether the intelligent oscillator needs to be adjusted, avoiding subjective assumptions and blind adjustments, and ensuring the scientificity and accuracy of the adjustment decision.

[0063] By setting clear adjustment strategies for different cell review status values, when the cell review status value is lower than the cell density reference value, it indicates that the intelligent oscillator's oscillation processing is reasonable, the cells are fully separated, and sufficient growth and proliferation are sufficient, and the effect is good, so the intelligent oscillator adjustment is not required. However, when the cell review status value is higher than the cell density reference value, it indicates that the intelligent oscillator's oscillation processing is unreasonable. There are cases where the cultured cells are not fully separated and not mixed with the nutrient solution, which is not suitable for cell growth and proliferation, and adjustment is required.

[0064] Clear reference values and adjustment strategies ensure a rational basis for adjustment under various cell review states, avoiding arbitrary and blind adjustments and improving the reliability and stability of the entire cell culture process. Furthermore, judgments based on preset reference values in the database ensure the scientific and effective nature of the adjustment strategy. Dynamically determining whether to adjust the intelligent oscillator based on changes in cell review state values can better meet cell growth requirements and improve the success rate and efficiency of cell culture.

[0065] When the intelligent oscillator needs to be adjusted, by adjusting the swing amplitude and swing frequency upwards, the distribution of cells and the supply of nutrients can be more effectively improved, the formation of cell clumps can be reduced, thereby optimizing the cell growth environment and improving cell yield and quality.

[0066] Furthermore, the review cell density is obtained and combined with the cell review status value analysis to obtain the equipment adjustment parameters of the intelligent oscillator. The specific steps include: based on the cell density reference value preset in the database, and comparing the difference with the review cell density, to obtain the review cell density difference ratio; matching based on the review cell density difference ratio to obtain the adjustment first reference execution value; matching based on the cell review status value to obtain the adjustment second reference execution value; coupling processing based on the adjustment first reference execution value and the adjustment second reference execution value to obtain the equipment adjustment parameters of the intelligent oscillator. The equipment adjustment parameters of the intelligent oscillator include the adjustment swing amplitude and adjustment swing frequency of the intelligent oscillator.

[0067] In this embodiment, the review cell density is compared with a preset cell density reference value to obtain a review cell density difference ratio. This difference ratio is then matched against a database to obtain a first reference execution value. Simultaneously, a second reference execution value is obtained based on the cell review status value and the database. The first reference execution value and the second reference execution value are then coupled together to obtain a device adjustment coupling value. Based on this device adjustment coupling value, specific adjustment parameters for the intelligent oscillator are obtained. This allows for flexible adaptation to different cell culture states, providing diverse adjustment strategies rather than a fixed approach, thereby better meeting the needs of cells at different growth stages.

[0068] Based on the preset cell density reference value in the database, the difference is compared with the reviewed cell density to obtain the review cell density difference ratio. The specific method is: subtracting the review cell density from the cell density reference value, and dividing the obtained difference by the cell density reference value to obtain the review cell density difference ratio.

[0069] Matching is performed based on the review cell density difference ratio to obtain the adjusted first reference execution value. The specific method is: obtain the preset review cell density difference ratio intervals and the adjustment preset reference execution values corresponding to the review cell density difference ratio intervals in the database, and compare them with the review cell density difference ratio. If the review cell density difference ratio is within a certain interval, obtain the adjustment preset reference execution value corresponding to the interval as the adjusted first reference execution value.

[0070] Matching is performed based on the cell review status value to obtain the adjusted second reference execution value. The specific method is: obtain the cell review status value intervals preset in the database and the adjusted preset second execution reference values corresponding to each cell review status value interval, and compare them with the cell review status value. If the cell review status value is within a certain interval, obtain the adjusted preset second execution reference value corresponding to the interval as the adjusted second reference execution value.

[0071] Based on the coupling processing of adjusting the first reference execution value and adjusting the second reference execution value, the device adjustment parameters of the intelligent oscillator are obtained. The specific method is: taking the average of the adjusting first reference execution value and the adjusting second reference execution value to obtain the device adjustment parameters of the intelligent oscillator, wherein the device adjustment parameters of the intelligent oscillator include the adjusted swing amplitude and the adjusted swing frequency of the intelligent oscillator.

[0072] It should also be noted that, adjusting the first reference execution value includes adjusting the first swing amplitude and the first swing frequency of the intelligent oscillator, and adjusting the second reference execution value includes adjusting the swing amplitude and the second swing frequency of the second intelligent oscillator.

[0073] Based on the device adjustment parameters of the intelligent oscillator, the swing amplitude of the intelligent oscillator is adjusted upward, and the swing frequency of the intelligent oscillator is adjusted upward. The specific method is: the swing amplitude of the intelligent oscillator is added to the adjusted swing amplitude of the intelligent oscillator to obtain the adjusted swing amplitude, and the swing frequency of the intelligent oscillator is added to the adjusted swing frequency to obtain the adjusted swing frequency.

[0074] Furthermore, it also includes obtaining the shear force in the cell culture process in real time after the stirring speed of the intelligent stirrer is adjusted, thereby determining whether to perform real-time adjustment of the equipment parameters. The specific method is: obtaining the shear force in the cell culture process and the shear force threshold preset in the database, and comparing them with the shear force in the cell culture process. If the shear force in the cell culture process is below the shear force threshold, the real-time adjustment of the equipment parameters is not performed. If the shear force in the cell culture process is greater than the shear force threshold, the real-time adjustment of the equipment parameters is performed; the real-time adjustment of the equipment parameters is performed, and the specific method is to perform differential processing based on the shear force in the cell culture process and the shear force threshold to obtain the shear force exceeding threshold ratio; the working status of the intelligent stirrer and the intelligent oscillator is judged, and if only the intelligent stirrer is in working state, state, the real-time stirring speed of the intelligent stirrer is obtained, and the real-time stirring speed of the intelligent stirrer is slowed down based on the shear force exceeding threshold ratio; matching is performed based on the culture reference value to obtain the culture limit parameter set, and the culture limit parameter set includes the stirring speed lower limit value, the swing amplitude lower limit value and the swing frequency lower limit value; if the intelligent stirrer and the intelligent oscillator are both in working state, the real-time stirring speed of the intelligent stirrer, the real-time swing amplitude and the real-time swing frequency of the intelligent oscillator are obtained; based on the shear force exceeding threshold ratio, the real-time stirring speed of the intelligent stirrer is slowed down, but not lower than the stirring speed lower limit value, the real-time swing amplitude of the intelligent oscillator is slowed down, but not lower than the swing amplitude lower limit value, and the real-time swing frequency of the intelligent oscillator is slowed down, but not lower than the swing frequency lower limit value.

[0075] In this example, by acquiring shear force during cell culture in real time and comparing it with a preset shear force threshold, it is possible to promptly detect whether shear force exceeds a safe range, preventing damage to cells caused by excessive shear force, thereby protecting healthy cell growth. When the shear force exceeds the threshold, differential processing is performed based on the shear force exceeding the threshold, accurately determining the device parameters that need to be adjusted and the adjustment range, avoiding the adverse effects that may arise from blind adjustments and ensuring the effectiveness and rationality of the adjustments.

[0076] By analyzing the shear forces during the cell culture process in real time (either the intelligent stirrer alone or both the intelligent stirrer and the intelligent oscillator), the system can adjust the parameters of the automated equipment in real time to prevent cell damage caused by excessive shear forces. This allows the automated equipment to adapt to different operating conditions, improving its adaptability and practicality. By simultaneously adjusting the stirring speed of the intelligent stirrer and the swing amplitude and frequency of the intelligent oscillator, the cell culture environment can be comprehensively optimized, reducing damage to cells caused by excessive shear forces while also improving cell distribution and nutrient supply, providing more suitable growth conditions for cells. Clear threshold settings and adjustment strategies ensure a reasonable basis for adjustment under various shear force conditions, avoiding arbitrary and blind adjustments and improving the reliability and stability of the entire cell culture process. Furthermore, the thresholds and adjustment strategies preset in the database ensure the scientific and effective nature of the adjustments.

[0077] If the shear force in the cell culture process is greater than the shear force threshold, the equipment parameters are adjusted in real time. Based on the shear force exceeding the threshold ratio, the real-time stirring speed of the intelligent stirrer is reduced, the real-time swing amplitude of the intelligent oscillator is reduced, and the real-time swing frequency of the intelligent oscillator is reduced. This can avoid excessive shear force and damage to cell activity. When making adjustments, if the intelligent stirrer and the intelligent oscillator are in working state at the same time, the speed of these two devices are reduced at the same time. The specific adjustment size is adjusted according to the shear force exceeding the threshold ratio. For example: (1) If only the intelligent stirrer is in operation at this time, then according to the intelligent stirrer The real-time stirring speed of the stirrer is multiplied by the shear force exceeding threshold ratio, and the shear adjustment speed of the intelligent stirrer is obtained by subtracting the product of the real-time stirring speed of the intelligent stirrer and the shear force exceeding threshold ratio from the real-time stirring speed of the intelligent stirrer at this time. The stirring is performed according to the shear adjustment speed of the intelligent stirrer. It should be noted that the shear adjustment speed must be above the lower limit of the stirring speed. If the calculated shear adjustment speed is less than the lower limit of the stirring speed, the shear adjustment speed at this time is set to the lower limit of the stirring speed. At this time, the shear force in the cell culture process is detected again, and the steps of the equipment adjustment judgment module and the oscillation adjustment module are repeatedly executed for adjustment.

[0078] (2) If the intelligent stirrer and the intelligent oscillator are in operation at the same time, the stirring speed of the intelligent stirrer is adjusted in the same way as in step (1), and the swing amplitude and swing frequency of the intelligent oscillator are adjusted at the same time. The specific adjustment method is to multiply the swing amplitude of the intelligent oscillator by the shear force exceeding threshold ratio, and subtract the product of the swing amplitude of the intelligent oscillator and the shear force exceeding threshold ratio from the swing amplitude of the intelligent oscillator at this time to obtain the shear adjustment swing amplitude of the intelligent oscillator, and then swing based on the shear adjustment swing amplitude of the intelligent oscillator.

[0079] The swing frequency of the intelligent oscillator is multiplied by the shear force exceeding threshold ratio, and the product of the swing frequency of the intelligent oscillator and the shear force exceeding threshold ratio is subtracted from the swing frequency of the intelligent oscillator at this time to obtain the shear adjustment swing frequency of the intelligent oscillator, and the oscillation is performed based on the shear adjustment swing frequency of the intelligent oscillator. It should be noted that the swing amplitude and swing frequency of the intelligent oscillator must be above the swing amplitude lower limit value and the swing frequency lower limit value. If the calculated shear adjustment swing amplitude is less than the stirring speed lower limit value, the shear adjustment swing amplitude at this time is set to the shear adjustment swing amplitude lower limit value. At this time, the shear force in the cell culture process is detected again, and the steps of the equipment adjustment determination module and the oscillation adjustment module are repeatedly executed for adjustment; if the calculated shear adjustment swing frequency is less than the stirring speed lower limit value, the shear adjustment swing frequency at this time is set to the shear adjustment swing frequency lower limit value. At this time, the shear force in the cell culture process is detected again, and the steps of the equipment adjustment determination module and the oscillation adjustment module are repeatedly executed for adjustment.

[0080] It should be noted that the real-time adjustment of the equipment parameters is performed by performing differential processing based on the shear force in the cell culture process and the shear force threshold to obtain the shear force exceeding threshold ratio. The specific method is: performing differential processing on the shear force in the cell culture process and the shear force threshold, and dividing the difference by the shear force threshold to obtain the shear force exceeding threshold ratio.

[0081] like Figure 2FIG. 1 is a schematic diagram of the structure of an artificial intelligence cell culture monitoring system provided in an embodiment of the present application. The artificial intelligence cell culture monitoring system provided in an embodiment of the present application includes: a cell culture judgment module, an initial culture module, an intelligent stirring execution module, a review and adjustment judgment module, and a stirring adjustment module. The cell culture judgment module is configured to, when the intelligent terminal receives a cell proliferation signal, perform cell activity detection based on the initial cells in the bioreactor to thereby determine whether to perform intelligent assisted adjustment. The initial culture module is configured to, if intelligent assisted adjustment is to be performed, obtain the size parameters and cell activity density of the bioreactor, and analyze to obtain a preset stirring speed and a set of culture-limited parameters. The intelligent stirring execution module is configured to cause the intelligent stirrer to perform stirring based on the preset stirring speed, and obtain cell density and cell state parameters at a preset sampling interval, and analyze to obtain a cell agglomeration impact value. The review and adjustment judgment module is configured to determine whether to perform review and adjustment based on the cell density and cell agglomeration impact value. If review and adjustment is not to be performed, an intelligent assisted adjustment end signal is sent to the intelligent terminal. If review and adjustment is to be performed, an assisted adjustment judgment result is obtained, and the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator are adjusted accordingly. The stirring adjustment module is used to obtain the cell review state parameters, analyze the cell review state value, and adjust the intelligent stirrer accordingly.

[0082] In summary, this embodiment performs cell activity detection on the initial cells in the bioreactor to determine whether to perform intelligent assisted adjustment. When performing intelligent assisted adjustment, the size parameters and cell activity density of the bioreactor are obtained, and the preset stirring speed and culture limit parameter set are analyzed to determine the appropriate stirring speed and culture parameters, thereby achieving precise control and personalized optimization of the cell culture process, and effectively solving the problem of cell damage caused by the failure of intelligent devices to make timely adaptive adjustments during the cell culture process in the prior art.

[0083] Those skilled in the art will appreciate that embodiments of the present invention may be provided as methods, systems, or computer program products. Thus, the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment, or an embodiment combining software and hardware aspects. Furthermore, the present invention may take the form of a computer program product implemented on one or more computer-usable storage media (including but not limited to magnetic disk storage, CD-ROM, optical storage, etc.) containing computer-usable program code.

[0084] The present invention is described with reference to flowcharts and / or block diagrams of methods, devices (systems), and computer program products according to embodiments of the present invention. It should be understood that each process and / or block in the flowcharts and / or block diagrams, as well as combinations of processes and / or blocks in the flowcharts and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, a special-purpose computer, an embedded processor, or other programmable data processing device to produce a machine, so that the instructions executed by the processor of the computer or other programmable data processing device generate instructions for implementing the processes in the flowcharts and / or block diagrams. Figure 1 a process or multiple processes and / or boxes Figure 1 A device that provides the functions specified in a block or multiple blocks.

[0085] These computer program instructions may also be stored in a computer readable memory that can direct a computer or other programmable data processing device to work in a specific manner, so that the instructions stored in the computer readable memory produce an article of manufacture comprising an instruction device, which implements the process Figure 1 a process or multiple processes and / or boxes Figure 1 The function specified in one or more boxes.

[0086] These computer program instructions can also be loaded onto a computer or other programmable data processing device so that a series of operational steps are executed on the computer or other programmable device to produce a computer-implemented process, thereby providing the instructions executed on the computer or other programmable device for implementing the process. Figure 1 a process or multiple processes and / or boxes Figure 1 A step that specifies a function in one or more boxes.

[0087] Although the preferred embodiments of the present invention have been described, those skilled in the art may make additional changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0088] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. An artificial intelligence cell culture monitoring method, characterized in that: The following steps are involved: S1. When the intelligent terminal receives the cell proliferation signal, it performs cell activity detection based on the initial cells in the bioreactor to determine whether to perform intelligent assisted adjustment; S2. If intelligent assisted adjustment is performed, the size parameters and cell activity density of the bioreactor are obtained, and a preset stirring speed and culture limit parameter set are obtained by analysis; S3. The intelligent stirrer performs stirring based on a preset stirring speed, and obtains cell density and cell state parameters according to a preset sampling interval, and analyzes and obtains a cell agglomerate influence value; wherein, obtaining the cell density and cell state parameters, and analyzing and obtaining the cell agglomerate influence value, specifically comprises the following steps: obtaining cell state parameters, the cell state parameters including the size of each cell agglomerate, the number of cell agglomerates, and the proportion of oversized cell agglomerates; obtaining a preset cell agglomerate allowable set in a database, performing a difference analysis between the cell density and the cell density reference value, performing a difference analysis between the size of each cell agglomerate and the cell agglomerate size reference value, introducing corresponding influencing factors, and fusing the proportion of oversized cell agglomerates with the influencing factor of the unit oversized cell agglomerate proportion, and fusing the number of cell agglomerates with the influencing factor of the unit cell agglomerate number to obtain the cell agglomerate influence value; S4. Determine whether to perform review adjustment based on the analysis of cell density and cell agglomeration impact value. If review adjustment is not performed, send an intelligent auxiliary adjustment end signal to the intelligent terminal. If review adjustment is performed, obtain the auxiliary adjustment determination result, and adjust the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator according to the settings; S5, obtaining cell review status parameters, analyzing to obtain cell review status values, and adjusting the intelligent stirrer accordingly; The cell review status parameters include the number of reviewed cell clusters, the proportion of reviewed over-specification cell clusters, and the reviewed average cell cluster size.

2. The artificial intelligence cell culture monitoring method according to claim 1, characterized in that: The cell activity detection is performed based on the initial cells in the bioreactor to determine whether to perform intelligent auxiliary adjustment. The specific steps include: Based on the initial cells in the bioreactor, cells are pre-stirred at a set pre-stirring speed, and the cell density after the pre-stirring is obtained and marked as the cell activity density; The initial cell density in the bioreactor is obtained and the difference is processed with the cell activity density to obtain the culture difference, which is then compared with the preset termination cell density in the database. If the culture difference is above the termination cell density, intelligent assisted adjustment is performed. If the culture difference is less than the termination cell density, intelligent assisted adjustment is not performed and an early warning reminder is issued.

3. The artificial intelligence cell culture monitoring method according to claim 1, characterized in that: The steps of obtaining the size parameters and cell activity density of the bioreactor and analyzing to obtain the preset stirring speed and culture limit parameter set include: Obtaining dimensional parameters of the bioreactor, wherein the dimensional parameters of the bioreactor include a diameter of the bioreactor and a diameter of a stirring blade; Obtain the preset data reference set in the data, and analyze the difference between it and the size parameters of the bioreactor and the cell activity density to obtain the culture reference value; Matching is performed based on the culture reference value to obtain a preset stirring speed; The data reference set includes an ideal cell activity density, a unit bioreactor diameter influence factor, and a unit stirring blade diameter influence factor; The culture reference value is obtained by evaluating the degree of coupling between the diameter of the bioreactor and the diameter of the stirring blade and the unit bioreactor diameter influencing factor and the unit stirring blade diameter influencing factor, respectively, and after coupling with the degree of difference between the cell activity density and the ideal cell activity density, introducing the corresponding influence weight.

4. The artificial intelligence cell culture monitoring method according to claim 1, characterized in that: The specific steps of determining whether to perform review adjustment based on the analysis of cell density and cell cluster impact value include: Obtain the cell cluster impact threshold and cell density reference value preset in the database; Based on the comparison between the cell density reference value and the cell density, and based on the comparison between the cell clump influence threshold and the cell clump influence value, if the cell density is greater than the cell density reference value and at the same time the cell clump influence value is below the cell clump influence threshold, no review adjustment will be performed; otherwise, review adjustment will be performed.

5. The artificial intelligence cell culture monitoring method according to claim 1, characterized in that: If the review adjustment is performed, the auxiliary adjustment determination result is obtained, and the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator are adjusted according to the settings. The specific steps include: If a review adjustment is performed, the cell density is compared with the cell density reference value, and the cell clump impact value is compared with the cell clump impact threshold value; If the cell density is below the cell density reference value and the cell clump impact value is greater than the cell clump impact threshold, the analysis obtains a first auxiliary adjustment determination result, which is to increase the stirring speed of the intelligent stirrer and start the intelligent oscillator; If the cell density is below the cell density reference value and the cell clump influence value is below the cell clump influence threshold, the analysis obtains a second auxiliary adjustment determination result, wherein the second auxiliary adjustment determination result is a constant intelligent stirrer stirring speed and the intelligent oscillator is started; If the cell density is greater than the cell density reference value, and the cell clump influence value is greater than the cell clump influence threshold, the analysis obtains a third auxiliary adjustment determination result, wherein the third auxiliary adjustment determination result is to reduce the stirring speed of the intelligent stirrer and start the intelligent oscillator; Based on the auxiliary adjustment judgment result and the cell agglomerate influence value, the stirring speed of the intelligent stirrer and the device parameters of the intelligent oscillator are adjusted according to the settings.

6. The artificial intelligence cell culture monitoring method according to claim 5, characterized in that: The method of adjusting the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator based on the auxiliary adjustment judgment result and the cell agglomeration influence value specifically includes the following steps: Performing difference processing based on the cell density reference value and the cell density to obtain a density difference, and performing matching based on the density difference to obtain a stirring speed of the first preset intelligent stirrer and equipment parameters of the first preset intelligent oscillator; Performing difference processing based on the cell agglomerate influence threshold and the cell agglomerate influence value to obtain a cell agglomerate difference, and performing matching based on the cell agglomerate difference to obtain a stirring speed of a second preset intelligent stirrer and equipment parameters of a second preset intelligent oscillator; If the auxiliary adjustment determination result is the first auxiliary adjustment determination result, the stirring speed of the first preset intelligent stirrer and the stirring speed of the second preset intelligent stirrer are averaged to obtain the stirring speed of the set adjustment intelligent stirrer, and the device parameters of the first preset intelligent oscillator and the device parameters of the second preset intelligent oscillator are averaged to obtain the device parameters of the intelligent oscillator; If the auxiliary adjustment determination result is the second auxiliary adjustment determination result, obtaining the stirring speed preset in the database as the preset stirring speed for adjusting the intelligent stirrer; If the auxiliary adjustment determination result is the third auxiliary adjustment determination result, the stirring speed of the second preset intelligent stirrer and the device parameters of the second preset intelligent oscillator are used as settings to adjust the stirring speed of the intelligent stirrer and the device parameters of the intelligent oscillator; The device parameters of the intelligent oscillator include the swing amplitude and the swing frequency of the intelligent oscillator.

7. The artificial intelligence cell culture monitoring method according to claim 1, characterized in that: The cell review state parameter is obtained and analyzed to obtain the cell review state value, thereby adjusting the intelligent stirrer accordingly. The specific method is as follows: Get cell review status parameters; Obtain the preset cell cluster review permission set in the database, and perform differential analysis with the cell review status parameter to obtain the cell review status value; The cell mass review permission set includes the unit review cell mass number influencing factor, the unit review over-specification cell mass ratio influencing factor and the review cell mass size reference value; The cell review status value is obtained by evaluating the coupling degree between the number of reviewed cell clusters and the proportion of reviewed oversized cell clusters and the influencing factor of the number of reviewed cell clusters and the influencing factor of the proportion of unit reviewed oversized cell clusters, and combining the difference between the average size of the reviewed cell clusters and the reference value of the reviewed cell cluster size, and then introducing the corresponding influence weight to obtain the cell review status value; Based on the comparison between the cell density reference value and the review cell density, and based on the comparison between the cell review state threshold value and the cell review state value, if the review cell density is greater than the cell density reference value, and at the same time the cell review state value is less than the cell review state threshold value, then an intelligent auxiliary adjustment end signal is sent to the intelligent terminal, otherwise the intelligent oscillator is adjusted; The adjustment of the intelligent oscillator is performed by obtaining the review cell density and combining it with the cell review status value analysis to obtain the device adjustment parameters of the intelligent oscillator, and based on the device adjustment parameters of the intelligent oscillator, the swing amplitude of the intelligent oscillator is adjusted upward, and the swing frequency of the intelligent oscillator is adjusted upward.

8. The artificial intelligence cell culture monitoring method according to claim 7, characterized in that: The steps of obtaining the review cell density and analyzing the cell review state value to obtain the device adjustment parameters of the intelligent oscillator include: Based on the preset cell density reference value in the database, the difference is compared with the review cell density to obtain the review cell density difference ratio; Matching is performed based on the reviewed cell density difference ratio to obtain an adjusted first reference execution value; Perform matching based on the cell review state value to obtain an adjusted second reference execution value; Based on the coupled processing of adjusting the first reference execution value and adjusting the second reference execution value, the device adjustment parameters of the intelligent oscillator are obtained, and the device adjustment parameters of the intelligent oscillator include the adjusted swing amplitude and the adjusted swing frequency of the intelligent oscillator.

9. The artificial intelligence cell culture monitoring method according to claim 1, characterized in that: It also includes obtaining the shear force in the cell culture process in real time after adjusting the stirring speed of the intelligent stirrer, thereby determining whether to adjust the equipment parameters in real time. The specific method is as follows: Obtaining the shear force during the cell culture process and a shear force threshold preset in a database, and comparing the two with the shear force during the cell culture process; if the shear force during the cell culture process is below the shear force threshold, no real-time adjustment of the device parameters is performed; if the shear force during the cell culture process is greater than the shear force threshold, real-time adjustment of the device parameters is performed; The execution device parameters are adjusted in real time, specifically by performing differential processing based on the shear force and the shear force threshold during the cell culture process to obtain the shear force exceeding threshold ratio; The working status of the intelligent stirrer and the intelligent oscillator is judged. If only the intelligent stirrer is in the working state, the real-time stirring speed of the intelligent stirrer is obtained, and the real-time stirring speed of the intelligent stirrer is reduced based on the shear force exceeding the threshold ratio. Matching is performed based on the culture reference value to obtain a culture limit parameter set, wherein the culture limit parameter set includes a stirring speed lower limit value, a swing amplitude lower limit value, and a swing frequency lower limit value; If the intelligent stirrer and the intelligent oscillator are both in working state, the real-time stirring speed of the intelligent stirrer, the real-time swing amplitude and the real-time swing frequency of the intelligent oscillator are obtained; Based on the shear force exceeding the threshold ratio, the real-time stirring speed of the intelligent stirrer is reduced, but not lower than the lower limit of the stirring speed; the real-time swing amplitude of the intelligent oscillator is reduced, but not lower than the lower limit of the swing amplitude; the real-time swing frequency of the intelligent oscillator is reduced, but not lower than the lower limit of the swing frequency.

10. A system using an artificial intelligence cell culture monitoring method according to any one of claims 1 to 9, characterized in that: include: Cell culture judgment module, initial culture module, intelligent stirring execution module, review and adjustment judgment module and stirring adjustment module; The cell culture judgment module is used to detect cell activity based on the initial cells in the bioreactor after the intelligent terminal receives the cell proliferation signal, thereby determining whether to perform intelligent auxiliary adjustment; The initial culture module is used to obtain the size parameters and cell activity density of the bioreactor if intelligent assisted adjustment is performed, and to analyze and obtain a preset stirring speed and a culture limit parameter set; The intelligent stirring execution module is used for the intelligent stirrer to perform stirring based on a preset stirring speed, and obtain cell density and cell state parameters according to a preset sampling interval, and analyze and obtain the cell agglomerate influence value; wherein, obtaining the cell density and cell state parameters and analyzing and obtaining the cell agglomerate influence value specifically comprises the following steps: obtaining cell state parameters, the cell state parameters including the size of each cell agglomerate, the number of cell agglomerates and the proportion of oversized cell agglomerates; obtaining a preset cell agglomerate allowable set in a database, performing a difference analysis between the cell density and the cell density reference value, performing a difference analysis between the size of each cell agglomerate and the cell agglomerate size reference value, introducing the corresponding influencing factors, and fusing the proportion of oversized cell agglomerates with the influencing factor of the unit oversized cell agglomerate proportion, and fusing the number of cell agglomerates with the influencing factor of the unit cell agglomerate number to obtain the cell agglomerate influence value; The review adjustment determination module is used to determine whether to perform review adjustment based on the analysis of cell density and cell agglomeration influence value. If review adjustment is not performed, an intelligent auxiliary adjustment end signal is sent to the intelligent terminal. If review adjustment is performed, an auxiliary adjustment determination result is obtained, and the stirring speed of the intelligent stirrer and the equipment parameters of the intelligent oscillator are adjusted according to the settings; The stirring adjustment module is used to obtain the cell review state parameters, analyze and obtain the cell review state value, and adjust the intelligent stirrer accordingly.

Citation Information

Patent Citations

  • Cell culture monitoring method and system based on artificial intelligence

    CN117421691B

  • A new cell culture method with controlled environment

    CN117932382B

  • Automated Cell Culturing

    CN110499252A

  • Continuous cell culture system and method

    CN118086050A