Intelligent feedback feeding control system based on substrate concentration on-line detection in fermentation process

By using an online biosensor analyzer to detect the substrate concentration in the fermentation system and perform intelligent feedback feeding, the problem of lagging substrate concentration detection data and inaccurate feeding control in the existing technology is solved, and the fermentation process is efficient and stable. and high quality production.

CN119331726AActive Publication Date: 2025-01-21NANJING TECH UNIV
View PDF 7 Cites 0 Cited by

Patent Information

Application Number
CN202411498909.4
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-10-25
Publication Date
2025-01-21
Estimated Expiration
2044-10-25

AI Technical Summary

Technical Problem

There is a large lag in the detection data of substrate concentration during the existing fermentation process, and the feed control method is inaccurate, resulting in excessive or insufficient nutrients, affecting the metabolic activities of microbial products and the quality and yield of fermentation products.

Method used

Use an online biosensor analyzer to detect the substrate concentration in the fermentation system, and automatically calculate the substrate consumption rate through the host computer control system, predict the substrate concentration in the next cycle, and compare the predicted value with the feeding target concentration. If it is lower than the target Then intelligent feedback feeding is carried out, and the feeding is automatically carried out through the peristaltic pump.

Benefits of technology

It achieves real-time monitoring of substrate concentration and precise feeding during the fermentation process, improves fermentation efficiency and product quality, reduces manual intervention and resource waste, and reduces production costs.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN119331726A_ABST
    Figure CN119331726A_ABST
Patent Text Reader

Abstract

The invention discloses an intelligent feedback feeding control system based on substrate concentration on-line detection in a fermentation process, which is characterized in that the concentration of a substrate in a bioreactor is detected through a biosensing analyzer, and a detection result is transmitted to an upper computer control system through serial port communication. The upper computer control system reads the bioreactor weight data provided by the metering scale, automatically calculates the substrate consumption rate according to the substrate concentration data, predicts the substrate concentration data at the next monitoring time point, and compares the substrate concentration data with the preset feeding target concentration. And when material supplementation is needed at the next monitoring time point, the system transmits volume data of the required material supplementation liquid to the peristaltic pump, and the peristaltic pump automatically pumps the material supplementation liquid into the bioreactor according to an instruction, so that feedback material supplementation in the fermentation process is completed. According to the system, manual intervention is reduced, the production cost is reduced, the defect that materials are supplemented in the fermentation process according to experience is overcome, and the microbial fermentation production efficiency and the product quality are improved.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] The present invention relates to the technical field of online monitoring and control of microbial fermentation processes, and specifically to a control system that utilizes an online biosensor analyzer to achieve online detection of substrate concentration in a fermentation system, and then performs intelligent feedback and feeding of the biological fermentation process. Background Art

[0002] Microbial fermentation is a complex biochemical process that involves the ability of various microorganisms such as bacteria, fungi, yeast, etc. to decompose organic matter or synthesize specific compounds under specific conditions. During the fermentation process, microorganisms use carbon sources, nitrogen sources and other nutrients in the culture medium to carry out metabolic activities and produce the desired products. These products can be valuable industrial products such as antibiotics, amino acids, enzymes, vitamins, organic acids, biofuels (such as ethanol), etc.

[0003] During the fermentation process, microorganisms will go through four stages: lag phase, logarithmic growth phase, stable phase and decay phase. The lag phase is the stage when microorganisms adapt to the new environment; the logarithmic growth phase is the period of rapid microbial proliferation; the stable phase is the period when the number of cells reaches the maximum and the product accumulates the most; the decay phase is the process in which microorganisms begin to die after the nutrients are exhausted. The improvement of fermentation efficiency mainly depends on the optimized management of the logarithmic growth phase and the stable phase. Therefore, online monitoring in these two stages is very necessary, which helps to adjust the fermentation conditions in time and maintain the optimal growth state of microorganisms, thereby improving the yield and quality of the product. Most of the existing fermentation processes rely on offline sampling and analysis. The data obtained by this method has a lag, that is, the detected concentration data is actually the result of a certain moment in the past, which leads to the fact that when problems are found in the fermentation process, the best adjustment time has often been missed. Therefore, the traditional feeding strategy often determines when to feed and how much to feed based on empirical values. This feeding method is prone to excessive or insufficient nutrients, affecting the metabolic activities of microorganisms, and even causing the accumulation of metabolic byproducts, further affecting the quality and yield of fermentation products. The fermentation process still requires frequent manual monitoring and adjustment, which not only increases the labor intensity, but also the inconsistency of manual operation will lead to instability in the fermentation process, affecting the consistency and repeatability of the product. In order to overcome these problems, it is necessary to develop a new online monitoring and intelligent feeding control system, which can detect the changes of key parameters in the fermentation process in real time, predict in advance and adjust the feeding strategy in time, so as to ensure the stability and efficiency of the fermentation process. Summary of the invention

[0004] Purpose of the invention: The purpose of the present invention is to overcome the shortcomings of large lag in substrate concentration detection data in existing fermentation processes and inaccurate control of existing feeding control methods, and to propose an intelligent feedback feeding control system that can detect substrate concentration in a fermentation system online and predict feeding based on the detection results.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is as follows: An intelligent feedback feeding control system based on online detection of substrate concentration during fermentation, the system is composed of a biosensor analyzer, a bioreactor, a peristaltic pump, a metering scale and a host computer control system to form a closed loop, the biosensor analyzer and the metering scale are used as control system data input components, the peristaltic pump is used as a control system data output component, the input and output components use serial communication for data interaction and collaborative control of the substrate concentration in the bioreactor; Among them, a biosensor analyzer is used to detect the substrate concentration in the bioreactor and transmit the result to the host computer control system through serial communication. At the same time, the host computer control system reads the bioreactor weight data weighed by the measuring scale, automatically calculates the substrate consumption rate according to the substrate concentration data, and predicts the substrate concentration data at the next monitoring time point, and compares the predicted substrate concentration data with the feed target concentration data. If feed is required at the next monitoring time point, the required feed liquid volume data will be transmitted to the peristaltic pump, and the peristaltic pump automatically pumps the feed liquid into the bioreactor, thereby completing the feedback feeding of the fermentation process.

[0006] Specifically, the host control system pre-sets the detection cycle F (h) of the fermentation process, the feedback feed concentration control target value c r (g / L), feed control range coefficient K (%), substrate feed solution concentration c f (g / L), feed peristaltic pump flow rate u p (L / h), after setting the initial parameters, the biosensor analyzer will detect the substrate concentration according to the detection cycle F (h) and transmit the data to the control system. At the same time, the weighing scale transmits the volume change of the bioreactor when the substrate concentration result comes out to the control system. After receiving the two sets of substrate concentration data, the control system automatically calculates the substrate concentration consumption rate v n , the relationship between the substrate concentration consumption rate and substrate concentration data during the fermentation process is: (1); Among them, u n is the substrate consumption rate between two cycles, c n-1 is the substrate concentration of the previous cycle, V n-1 is the volume of the fermentation liquid in the bioreactor in the previous cycle, c n is the substrate concentration of this cycle, V n is the volume of fermentation liquid in the bioreactor in this cycle, t n -t n-1 It is the time difference between this cycle and the previous cycle.

[0007] Specifically, after the calculation of the substrate concentration consumption rate is completed, the predicted value of the substrate concentration in the next cycle is calculated, and the predicted value of the substrate concentration in the next cycle is compared with the feedback feed concentration control target value c. r (g / L) comparison, if the predicted value of the substrate concentration in the next cycle is lower than the feedback feed concentration control target value c r (g / L), then feeding is required in the next cycle, and the prediction of the feeding time point in the feeding cycle needs to be started; if the predicted value of the substrate concentration in the next cycle is not lower than the feedback feeding concentration control target value c r (g / L), the biosensor analyzer detects the substrate concentration in the bioreactor in the next cycle, and continues to calculate the substrate concentration consumption rate in the last two cycles and the predicted value of the substrate concentration in the next cycle and feedback feed concentration control target value c r (g / L) comparison, until the predicted value of substrate concentration in a certain cycle is lower than the feedback feed concentration control target value c r (g / L).

[0008] Specifically, the relationship between the predicted value of the substrate concentration in the next cycle of the fermentation process and the substrate concentration in the previous cycle is: (2); Among them, c n+1 is the predicted value of substrate concentration in the next cycle, c n is the substrate concentration of this cycle, V n is the volume of the fermentation liquid in the bioreactor in this cycle, u n is the substrate consumption rate between two cycles, V n+1 is the volume of the fermentation liquid in the bioreactor in the next cycle, t n+1 -t n It is the time difference between the next cycle and this cycle.

[0009] Specifically, when feeding is required in the next cycle, the cycle is defined as the feeding cycle, and the feeding time point is calculated within the feeding cycle, that is, the specific time point when the substrate concentration is lower than the target concentration within the cycle. The relationship between the predicted value of the feeding time point within the feeding cycle of the fermentation process and the target feeding value is: (3); in, is the predicted value of the feeding time point in the feeding cycle of the fermentation process, c n is the substrate concentration of this cycle, V n is the volume of fermentation liquid in the bioreactor in this cycle, c r is the target value for the control of the feeding concentration, K is the feeding control range coefficient, u n is the substrate consumption rate between two cycles, t n The time for this cycle.

[0010] Furthermore, after obtaining the feeding time point in the feeding cycle, the biosensor analyzer detects whether the substrate concentration in the bioreactor is lower than the feedback feeding concentration control target value c at this time point. r (g / L), if it is lower than the feedback feed concentration control target value c r (g / L), the feeding procedure is started, otherwise the substrate concentration consumption rate in the last two cycles and the predicted value of the substrate concentration in the next cycle are calculated and compared with the feedback feeding concentration control target value c r (g / L) comparison, until the predicted value of substrate concentration in a certain cycle is lower than the feedback feed concentration control target value c r (g / L), and calculate the feeding time point within the feeding cycle.

[0011] Specifically, the feeding program of the control system is mainly executed by the peristaltic pump. The control system calculates the running time of the peristaltic pump based on the existing data. After the running time of the peristaltic pump ends, the first fermentation process intelligently feedbacks the completion of feeding until the detection cycle ends. The relationship between the running time and the existing data is: (4); in, is the peristaltic pump running time, is the volume of fermentation liquid in the bioreactor at the feeding time point, is the substrate concentration in the bioreactor at the feeding time point, c r is the target value for feeding concentration control, K is the feeding control range coefficient, is the substrate consumption rate from the feeding time point to the current cycle, is the time difference between the feeding time point and the next cycle, c f is the feed solution concentration, u p Run the peristaltic pump flow rate for the feed.

[0012] Specifically, when entering the feeding cycle, the control system needs to calculate the new consumption rate based on the substrate concentration tested by the biosensor analyzer. The relationship between the consumption rate and the substrate concentration after the feeding cycle is: (5); in, is the substrate consumption rate from the feeding time point to the current cycle, c n is the substrate concentration of this cycle, V n is the volume of the fermentation liquid in the bioreactor in this cycle, is the volume of fermentation liquid in the bioreactor at the feeding time point, is the substrate concentration in the bioreactor at the feeding time point, It is the time difference between the feeding time point and the next cycle.

[0013] Specifically, the microbial growth process is divided into four stages: lag phase, logarithmic growth phase, stable phase and decay phase. In the lag phase and the early logarithmic growth phase of the microorganism, the substrate concentration data in the bioreactor is tested using a biosensor analyzer, and a consumption rate metabolic curve is established. Based on this data, the substrate concentration data in the next cycle is predicted, and it is determined whether it is lower than the target concentration for feeding. The peristaltic pump is driven in time to feed the feed to prevent the microorganism from entering the decay phase, so that the microorganism can normally produce the target substance and improve production efficiency.

[0014] Furthermore, the present invention also claims to protect the use of the above control system for automatic feeding in the fermentation process of brewer's yeast.

[0015] Compared with the prior art, the present invention has the following beneficial effects: The system of the present invention is a control system for intelligent feedback feeding based on online detection of substrate concentration during fermentation. Based on substrate concentration data detected by a biosensor analyzer, a substrate concentration consumption curve is constructed. The control system automatically predicts the feeding time point to perform feeding control work for fermentation production. Through online monitoring and intelligent feedback feeding, the efficiency of the fermentation process and product quality are improved. It has a pre-prediction function and a constant-speed feeding function, accurate control, good operation repeatability, so that the fermentation process is in a good process, reducing manual intervention, reducing production costs, overcoming the drawbacks of feeding the fermentation process based on experience, so that microbial fermentation production can be carried out efficiently, through precise control, reducing resource waste, achieving energy conservation and emission reduction, and promoting the engineering application level of optimizing feeding control in the fermentation process. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more clear.

[0017] Figure 1 It is a schematic diagram of a control system for intelligent feedback feeding based on online detection of substrate concentration during fermentation according to the present invention.

[0018] Figure 2 It is a flow chart of a control system for intelligent feedback feeding of substrate concentration online detection in the fermentation process of the present invention.

[0019] Figure 3 It is the glucose concentration of the fermentation broth detected by a biosensor analyzer during the fermentation process. DETAILED DESCRIPTION

[0020] The present invention can be better understood with reference to the following examples.

[0021] Combination Figure 1 and Figure 2As shown, the present invention is based on the intelligent feedback feeding control system for online detection of substrate concentration during fermentation, which mainly consists of a biosensor analyzer, a bioreactor, a peristaltic pump, a dosing scale and a host computer control system to form a closed loop. The biosensor analyzer and the dosing scale serve as data input components of the control system, and the peristaltic pump serves as a data output component of the control system. The input and output components use serial communication to perform data interaction and collaboratively control the substrate concentration in the bioreactor.

[0022] A biosensor analyzer is used to detect the substrate concentration in the bioreactor and transmit the result to the host computer control system through serial communication. At the same time, the host computer control system reads the bioreactor weight data weighed by the metering scale, automatically calculates the substrate consumption rate based on the substrate concentration data, and predicts the substrate concentration data at the next monitoring time point. The predicted substrate concentration data is compared with the feed target concentration data. If feed is required at the next monitoring time point, the required feed liquid volume data will be transmitted to the peristaltic pump, and the peristaltic pump automatically pumps the feed liquid into the bioreactor, thereby completing the feedback feeding of the fermentation process.

[0023] The host computer control system pre-sets the detection cycle F (h) of the fermentation process and the feedback feed concentration control target value c r (g / L), feed control range coefficient K (%), substrate feed solution concentration c f (g / L), feed peristaltic pump flow rate u p (L / h), after setting the initial parameters, the biosensor analyzer will detect the substrate concentration according to the detection cycle F (h) and transmit the data to the control system. At the same time, the weighing scale transmits the volume change of the bioreactor when the substrate concentration result comes out to the control system. After receiving the two sets of substrate concentration data, the control system automatically calculates the substrate concentration consumption rate v n , the relationship between the substrate concentration consumption rate and substrate concentration data during the fermentation process is: (1); Among them, u n is the substrate consumption rate between two cycles, c n-1 is the substrate concentration of the previous cycle, V n-1 is the volume of the fermentation liquid in the bioreactor in the previous cycle, c n is the substrate concentration of this cycle, V n is the volume of fermentation liquid in the bioreactor in this cycle, t n -t n-1 It is the time difference between this cycle and the previous cycle.

[0024] After the calculation of substrate concentration consumption rate is completed, the predicted value of substrate concentration in the next cycle is calculated, and the predicted value of substrate concentration in the next cycle is compared with the feedback feed concentration control target value c r(g / L) comparison, if the predicted value of the substrate concentration in the next cycle is lower than the feedback feed concentration control target value c r (g / L), then feeding is required in the next cycle, and the prediction of the feeding time point in the feeding cycle needs to be started; if the predicted value of the substrate concentration in the next cycle is not lower than the feedback feeding concentration control target value c r (g / L), the biosensor analyzer detects the substrate concentration in the bioreactor in the next cycle, and continues to calculate the substrate concentration consumption rate in the last two cycles and the predicted value of the substrate concentration in the next cycle and feedback feed concentration control target value c r (g / L) comparison, until the predicted value of substrate concentration in a certain cycle is lower than the feedback feed concentration control target value c r (g / L).

[0025] The relationship between the predicted value of the substrate concentration in the next cycle of the fermentation process and the substrate concentration in the previous cycle is: (2); Among them, c n+1 is the predicted value of substrate concentration in the next cycle, c n is the substrate concentration of this cycle, V n is the volume of the fermentation liquid in the bioreactor in this cycle, u n is the substrate consumption rate between two cycles, V n+1 is the volume of the fermentation liquid in the bioreactor in the next cycle, t n+1 -t n It is the time difference between the next cycle and this cycle.

[0026] When feeding is required in the next cycle, the cycle is defined as the feeding cycle. The feeding time point is calculated within the feeding cycle, that is, the specific time point when the substrate concentration is lower than the target concentration within the cycle. The relationship between the predicted value of the feeding time point within the feeding cycle of the fermentation process and the target feeding value is: (3); in, is the predicted value of the feeding time point in the feeding cycle of the fermentation process, c n is the substrate concentration of this cycle, V n is the volume of fermentation liquid in the bioreactor in this cycle, c r is the target value for the control of the feeding concentration, K is the feeding control range coefficient, u n is the substrate consumption rate between two cycles, t n The time for this cycle.

[0027] After obtaining the feeding time point within the feeding cycle, the biosensor analyzer detects whether the substrate concentration in the bioreactor is lower than the feedback feeding concentration control target value c at this time point. r(g / L), if it is lower than the feedback feed concentration control target value c r (g / L), the feeding procedure is started, otherwise the substrate concentration consumption rate in the last two cycles and the predicted value of the substrate concentration in the next cycle are calculated and compared with the feedback feeding concentration control target value c r (g / L) comparison, until the predicted value of substrate concentration in a certain cycle is lower than the feedback feed concentration control target value c r (g / L), and calculate the feeding time point within the feeding cycle.

[0028] The feeding program of the control system is mainly executed by the peristaltic pump. The control system calculates the running time of the peristaltic pump based on the existing data. After the running time of the peristaltic pump ends, the first fermentation process intelligently feedbacks the feeding completion until the detection cycle ends. The relationship between the running time and the existing data is: (4); in, is the peristaltic pump running time, is the volume of fermentation liquid in the bioreactor at the feeding time point, is the substrate concentration in the bioreactor at the feeding time point, c r is the target value for feeding concentration control, K is the feeding control range coefficient, is the substrate consumption rate from the feeding time point to the current cycle, is the time difference between the feeding time point and the next cycle, c f is the feed solution concentration, u p Run the peristaltic pump flow rate for the feed.

[0029] Entering the feeding cycle, the control system needs to calculate the new consumption rate based on the substrate concentration tested by the biosensor analyzer. The relationship between the consumption rate and the substrate concentration after the feeding cycle is: (5); in, is the substrate consumption rate from the feeding time point to the current cycle, c n is the substrate concentration of this cycle, V n is the volume of the fermentation liquid in the bioreactor in this cycle, is the volume of fermentation liquid in the bioreactor at the feeding time point, is the substrate concentration in the bioreactor at the feeding time point, It is the time difference between the feeding time point and the next cycle.

[0030] The present invention divides the microbial growth process into four stages: lag phase, logarithmic growth phase, stable phase and decay phase. In the lag phase and the early logarithmic growth phase of the microorganism, a biosensor analyzer is used to test the substrate concentration data in the bioreactor, and a consumption rate metabolic curve is established. The substrate concentration data in the next cycle is predicted based on the data, and it is judged whether it is lower than the target concentration of feeding, and the peristaltic pump is driven in time to feed to prevent the microorganism from entering the decay phase, so that the microorganism can normally produce the target substance and improve the production efficiency.

[0031] The control system is used in the measurement and control of the fermentation process of brewer's yeast to realize the intelligent regulation of the substrate concentration during the fermentation process. The initial concentration of glucose in the fermentation broth is 78.81g / L, and the concentration of glucose added by flow addition is 500g / L. The biosensor analyzer is used to detect the glucose concentration in the fermentation broth. After the detection is completed, the data is transmitted to the control system. At the same time, the weighing scale transmits the weight change of the bioreactor when the glucose concentration result comes out to the control system. After the control system receives the two sets of substrate concentration data, it calculates the substrate consumption rate in this cycle based on the two sets of substrate data, and determines whether the next cycle needs to be fed. If feeding is required, the control system calculates the feed amount and sends the calculated feed amount to the injection pump to complete the feeding operation. In the measurement and control of the fermentation process of brewer's yeast, the detection frequency of the biosensor analyzer is set to 30min, the target concentration is 26 g / L, the feed control range coefficient K (%) is 10, and the feed pump flow rate is 10ml / min. A control system based on intelligent feedback feeding based on online detection of substrate concentration during fermentation is adopted, such as Figure 3 It is the glucose concentration of the fermentation broth substrate detected by the biosensor analyzer during the fermentation process. Figure 3 It can be seen that the total fermentation time is 399 minutes, among which the glucose concentration drops rapidly from 0 to 314 minutes. During this period, the biosensor analyzer takes samples and detects every 30 minutes. The host computer analyzes the test results, but the host computer calculates that the substrate glucose concentration during this period is above the target concentration and does not need to be fed. In the following 314 to 399 minutes, the feeding cycle begins. Based on the data sampled at 284 minutes and 314 minutes, the host computer accurately predicts that the substrate glucose concentration in the fermentation broth will be lower than the target concentration at 323 minutes, and controls the biosensor analyzer to sample and detect at 323 minutes. The test result is 25.6g / L, which is lower than the target concentration, and the feeding begins. The host computer calculates the feeding volume to be 30mL and controls the peristaltic pump to feed. After the feeding is completed, the host computer controls the biosensor analyzer again to detect the substrate glucose concentration in the fermentation broth, and the result is 28.53g / L, which is within the feeding control range, and the first feeding is completed.

[0032] from Figure 3It can be seen that after the first feeding is completed, the host computer predicts that the substrate glucose concentration in the fermentation broth will be lower than the target concentration at 351 minutes based on the sugar consumption rate calculated by the sampling test results at 314 minutes and 323 minutes, and controls the biosensor analyzer to sample and test at 351 minutes. The test result is 25.18g / L, which is lower than the target concentration, and the feeding begins. The host computer calculates the feeding volume as 35.4mL and controls the peristaltic pump to feed. After the feeding is completed, the host computer controls the biosensor analyzer again to test the substrate glucose concentration in the fermentation broth, and the result is 28.81g / L, which is within the feeding control range. The second feeding is completed. Figure 3 It can be seen that after the second feeding is completed, the host computer predicts that the substrate glucose concentration in the fermentation broth will be lower than the target concentration at 386 minutes based on the sugar consumption rate calculated by the sampling test results at 329 minutes and 351 minutes, and controls the biosensor analyzer to sample and test at 386 minutes. The test result is 25.18 g / L, which is lower than the target concentration, and the feeding starts. The host computer calculates the feeding volume as 35.7 mL and controls the peristaltic pump to feed. After the feeding is completed, the host computer controls the biosensor analyzer again to detect the substrate glucose concentration in the fermentation broth, and the result is 28.59 g / L, which is within the feeding control range. The third feeding is completed.

[0033] Table 1 Data on the change of substrate glucose concentration and fermentation liquid volume over time in yeast fermentation experiment

[0034] In different fermentation systems, the feed control range coefficient K (%) needs to be appropriately adjusted according to the bacterial substrate consumption rate. If the substrate consumption rate is fast, the feed control range coefficient K (%) needs to be increased to allow sufficient time to complete the "detection-feeding-detection" process. If the substrate consumption rate is slow, the feed control range coefficient K (%) can be reduced to achieve more accurate feed control.

[0035] Existing feedback feeding control schemes all indirectly reflect the substrate consumption during the fermentation process based on the pH and dissolved oxygen of the fermentation liquid, which has large deviations and cannot meet the needs of high-precision fermentation feeding control. The intelligent feedback feeding control system based on online detection of substrate concentration during the fermentation process in the present invention adopts a substrate online detection feedback feeding scheme, which can adjust the feeding amount according to the different substrate consumption rates in each cycle during the fermentation, thereby meeting the needs of high-precision fermentation feeding control.

[0036] The intelligent feedback feeding control system based on online detection of substrate concentration during the fermentation process automatically corrects the feedback feeding control according to the iterative sugar consumption. Compared with the existing feeding method based on physicochemical parameters (pH, dissolved oxygen, etc.), it is more direct and efficient, has stronger adaptability to different fermentation systems, and can realize unmanned operation of the fermentation process. It has broad application prospects in the field of fermentation.

[0037] The present invention provides a concept and method of a control system for intelligent feedback feeding based on online detection of substrate concentration during fermentation. There are many methods and approaches to implement the technical solution. The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention. All components not specified in this embodiment can be implemented by existing technologies.

Claims

1. An intelligent feedback feeding control system based on online detection of substrate concentration during fermentation, characterized in that: The system consists of a biosensor analyzer, a bioreactor, a peristaltic pump, a dosing scale and a host computer control system to form a closed loop. The biosensor analyzer and the dosing scale serve as data input components of the control system, and the peristaltic pump serves as a data output component of the control system. The input and output components use serial communication to exchange data and coordinately control the substrate concentration in the bioreactor. Among them, a biosensor analyzer is used to detect the substrate concentration in the bioreactor and transmit the result to the host computer control system through serial communication. At the same time, the host computer control system reads the bioreactor weight data weighed by the measuring scale, automatically calculates the substrate consumption rate according to the substrate concentration data, and predicts the substrate concentration data at the next monitoring time point, and compares the predicted substrate concentration data with the feed target concentration data. If feed is required at the next monitoring time point, the required feed liquid volume data will be transmitted to the peristaltic pump, and the peristaltic pump automatically pumps the feed liquid into the bioreactor, thereby completing the feedback feeding of the fermentation process.

2. The intelligent feedback feeding control system based on online detection of substrate concentration during fermentation according to claim 1, characterized in that: The host computer control system pre-sets the detection cycle F (h) of the fermentation process and the feedback feed concentration control target value c r (g / L), feed control range coefficient K (%), substrate feed solution concentration c f (g / L), feed peristaltic pump flow rate u p (L / h), after setting the initial parameters, the biosensor analyzer will detect the substrate concentration according to the detection cycle F (h) and transmit the data to the control system. At the same time, the weighing scale transmits the volume change of the bioreactor when the substrate concentration result comes out to the control system. After receiving the two sets of substrate concentration data, the control system automatically calculates the substrate concentration consumption rate v n , the relationship between the substrate concentration consumption rate and substrate concentration data during the fermentation process is: (1); Among them, u n is the substrate consumption rate between two cycles, c n-1 is the substrate concentration of the previous cycle, V n-1 is the volume of the fermentation liquid in the bioreactor in the previous cycle, c n is the substrate concentration of this cycle, V n is the volume of fermentation liquid in the bioreactor in this cycle, t n -t n-1 It is the time difference between this cycle and the previous cycle.

3. The intelligent feedback feeding control system based on online detection of substrate concentration during fermentation according to claim 2, characterized in that: After the calculation of substrate concentration consumption rate is completed, the predicted value of substrate concentration in the next cycle is calculated, and the predicted value of substrate concentration in the next cycle is compared with the feedback feed concentration control target value c r (g / L) comparison, if the predicted value of the substrate concentration in the next cycle is lower than the feedback feed concentration control target value c r (g / L), then feeding is required in the next cycle, and the prediction of the feeding time point in the feeding cycle needs to be started; if the predicted value of the substrate concentration in the next cycle is not lower than the feedback feeding concentration control target value c r (g / L), the biosensor analyzer detects the substrate concentration in the bioreactor in the next cycle, and continues to calculate the substrate concentration consumption rate in the last two cycles and the predicted value of the substrate concentration in the next cycle and feedback feed concentration control target value c r (g / L) comparison, until the predicted value of substrate concentration in a certain period is lower than the feedback feed concentration control target value c r (g / L).

4. The intelligent feedback feeding control system based on online detection of substrate concentration during fermentation according to claim 3, characterized in that: The relationship between the predicted value of the substrate concentration in the next cycle of the fermentation process and the substrate concentration in the previous cycle is: (2); Among them, c n+1 is the predicted value of substrate concentration in the next cycle, c n is the substrate concentration of this cycle, V n is the volume of fermentation liquid in the bioreactor in this cycle, u n is the substrate consumption rate between two cycles, V n+1 is the volume of the fermentation liquid in the bioreactor in the next cycle, t n+1 -t n It is the time difference between the next cycle and this cycle.

5. The intelligent feedback feeding control system based on online detection of substrate concentration during fermentation according to claim 3, characterized in that: When feeding is required in the next cycle, the cycle is defined as the feeding cycle. The feeding time point is calculated within the feeding cycle, that is, the specific time point when the substrate concentration is lower than the target concentration within the cycle. The relationship between the predicted value of the feeding time point within the feeding cycle of the fermentation process and the target feeding value is: (3); in, is the predicted value of the feeding time point in the feeding cycle of the fermentation process, c n is the substrate concentration of this cycle, V n is the volume of the fermentation liquid in the bioreactor in this cycle, c r is the target value for the control of the feeding concentration, K is the feeding control range coefficient, u n is the substrate consumption rate between two cycles, t n The time for this cycle.

6. The intelligent feedback feeding control system based on online detection of substrate concentration during fermentation according to claim 5, characterized in that: After obtaining the feeding time point within the feeding cycle, the biosensor analyzer detects whether the substrate concentration in the bioreactor is lower than the feedback feeding concentration control target value c at this time point. r (g / L), if it is lower than the feedback feed concentration control target value c r (g / L), the feeding procedure is started, otherwise the substrate concentration consumption rate in the last two cycles and the predicted value of the substrate concentration in the next cycle are calculated and compared with the feedback feeding concentration control target value c r (g / L) comparison, until the predicted value of substrate concentration in a certain period is lower than the feedback feed concentration control target value c r (g / L), and calculate the feeding time point within the feeding cycle.

7. The intelligent feedback feeding control system based on online detection of substrate concentration during fermentation according to claim 6, characterized in that: The feeding program of the control system is mainly executed by the peristaltic pump. The control system calculates the running time of the peristaltic pump based on the existing data. After the running time of the peristaltic pump ends, the first fermentation process intelligently feedbacks the feeding completion until the detection cycle ends. The relationship between the running time and the existing data is: (4); in, is the peristaltic pump running time, is the volume of fermentation liquid in the bioreactor at the feeding time point, is the substrate concentration in the bioreactor at the feeding time point, c r is the target value for feeding concentration control, K is the feeding control range coefficient, is the substrate consumption rate from the feeding time point to the current cycle, is the time difference between the feeding time point and the next cycle, c f is the feed solution concentration, u p Run the peristaltic pump flow rate for the feed.

8. The intelligent feedback feeding control system based on online detection of substrate concentration during fermentation according to claim 7, characterized in that: Entering the feeding cycle, the control system needs to calculate the new consumption rate based on the substrate concentration tested by the biosensor analyzer. The relationship between the consumption rate and the substrate concentration after the feeding cycle is: (5); in, is the substrate consumption rate from the feeding time point to the current cycle, c n is the substrate concentration of this cycle, V n is the volume of the fermentation liquid in the bioreactor in this cycle, is the volume of fermentation liquid in the bioreactor at the feeding time point, is the substrate concentration in the bioreactor at the feeding time point, It is the time difference between the feeding time point and the next cycle.

9. The intelligent feedback feeding control system based on online detection of substrate concentration during fermentation according to claim 8, characterized in that: The microbial growth process is divided into four stages: lag phase, logarithmic growth phase, stable phase and decay phase. In the lag phase and the early logarithmic growth phase of the microorganism, the substrate concentration data in the bioreactor is tested using a biosensor analyzer, and a consumption rate metabolic curve is established. Based on this data, the substrate concentration data in the next cycle is predicted, and it is determined whether it is lower than the target feed concentration. The peristaltic pump is driven in time to feed the feed to prevent the microorganism from entering the decay phase, so that the microorganism can normally produce the target substance and improve production efficiency.

10. Use of the control system according to claim 1 for automatic feeding in a fermentation process of brewer's yeast.

Citation Information

Patent Citations

  • Simulated fermentation process

    CA2770702A1

  • A method for on-line optimization of a fed-batch fermentation unit to maximize the product yield

    CN101484572A

  • Feedback feeding control method and system based on multi-component concentration online detection

    CN115730500A

  • Fermentation control method, device and equipment and readable storage medium

    CN116640886A

  • Feedback feeding method and system based on improved exponential smoothing neural network model

    CN116751896A