Sterilization Control Method of Biological Reactor

Abstract

The present application relates to a sterilization control method for a bioreactor, including: when a first bioreactor is sterilized in air and a second bioreactor is fermented in biological fermentation, the second valve of the first bioreactor and the fourth valve of the second bioreactor are controlled to be opened, and the fourth valve of the first bioreactor and the second valve of the second bioreactor are controlled to be closed; when the first bioreactor is fermented in biological fermentation and the second bioreactor is sterilized in air, the fourth valve of the first bioreactor and the second valve of the second bioreactor are controlled to be opened, and the second valve of the first bioreactor and the fourth valve of the second bioreactor are controlled to be closed. The present invention improves the steam utilization rate, thereby reducing the waste of water resources and thermal resources as a whole, and solves the problem of low resource utilization rate in the current steam air sterilization method of reactors.

Description

Technical Field

[0001] The present application relates to the field of sterilization and disinfection, and in particular to a sterilization control method for a biological reactor. Background Art

[0002] At present, the common sterilization methods at home and abroad mainly include steam air sterilization, steam solid sterilization, and pressure solid sterilization. The traditional biological fermentation reactor uses steam air sterilization, and the air sterilization process ensures that the temperature is 121 degrees and maintained for 30 minutes. In the long run, this method consumes a huge amount of steam, and the consumed steam is discharged outdoors, resulting in a waste of resources. In addition, the current reactor and its sterilization method also have the following disadvantages: the cold spot of the reactor sterilization is usually located in an area that is difficult to be directly touched by steam or heat, or in an area where heat conduction is slow; the sensors inside the reactor are susceptible to interference signals during operation, and these interference signals come from the sensor itself, the working environment, and the interaction process between the sensor and other equipment; if the monitoring is not in place and the corresponding sterilization conditions are not met, the production progress will be affected.

[0003] The current steam air sterilization method for reactors has the problem of low resource utilization, and no effective solution has been proposed yet. Summary of the invention

[0004] The present invention provides a sterilization control method for a biological reactor to solve the problem of low resource utilization in the current steam air sterilization method for the reactor.

[0005] In a first aspect, the present invention provides a sterilization control method for a bioreactor, which is applied to a bioreactor group, wherein the bioreactor group includes two bioreactors, each of which includes a body and a jacket sleeved on the outside of the body, the body is provided with a first valve and a second valve, the jacket is provided with a third valve and a fourth valve, the two bioreactors are defined as a first bioreactor and a second bioreactor, the second valve of the first bioreactor is connected to the fourth valve of the second bioreactor, and the fourth valve of the first bioreactor is connected to the second valve of the second bioreactor;

[0006] The sterilization control method comprises:

[0007] When the first bioreactor is sterilized and the second bioreactor is fermented, the second valve of the first bioreactor and the fourth valve of the second bioreactor are controlled to be opened, and the fourth valve of the first bioreactor and the second valve of the second bioreactor are controlled to be closed;

[0008] When the first bioreactor is undergoing biological fermentation and the second bioreactor is undergoing air sterilization, the fourth valve of the first bioreactor and the second valve of the second bioreactor are controlled to be opened, and the second valve of the first bioreactor and the fourth valve of the second bioreactor are controlled to be closed.

[0009] In a second aspect, the present invention provides a method for sterilizing a bioreactor, wherein the bioreactor is controlled by the method for sterilizing a bioreactor described in the first aspect.

[0010] Compared with the related art, the sterilization control method of the bioreactor provided by the present invention connects some valves of two adjacent bioreactors. When one of the bioreactors is sterilized by air, its excess steam is discharged into the jacket of the other bioreactor to provide the heat required for biological fermentation. Compared with the prior art, in which the steam used for air sterilization is directly discharged out of the system, the present invention improves the steam utilization rate, thereby reducing the waste of water resources and thermal resources as a whole, and solves the problem of low resource utilization in the current steam air sterilization method of the reactor.

[0011] Details of one or more embodiments of the present application are set forth in the following drawings and description to make other features, objects, and advantages of the present application more readily apparent. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 Schematic diagram of valve connection of a bioreactor group in some embodiments of the present invention;

[0013] Figure 2 is a schematic diagram of the structure of a single biological reactor in some embodiments of the present invention;

[0014] Figure 3 Schematic diagram of air sterilization in some embodiments of the present invention. DETAILED DESCRIPTION

[0015] In order to more clearly understand the purpose, technical solutions and advantages of the present application, the present application is described and illustrated below in conjunction with the accompanying drawings and embodiments.

[0016] Unless otherwise defined, the technical terms or scientific terms involved in this application shall have the general meaning understood by people with general skills in the technical field to which this application belongs. The words "one", "a", "the", "these" and the like in this application do not indicate a quantitative limitation, and they may be singular or plural. The terms "include", "comprise", "have" and any variants thereof involved in this application are intended to cover non-exclusive inclusions; for example, a process, method and system, product or device comprising a series of steps or modules (units) is not limited to the listed steps or modules (units), but may include unlisted steps or modules (units), or may include other steps or modules (units) inherent to these processes, methods, products or devices. The words "connect", "connected", "coupled" and the like involved in this application are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. The "multiple" involved in this application refers to two or more. "And / or" describes the association relationship of associated objects, indicating that there may be three relationships, for example, "A and / or B" may mean: A exists alone, A and B exist at the same time, and B exists alone. Generally, the character " / " indicates that the objects associated with each other are in an "or" relationship. The terms "first", "second", "third", etc. in this application are only used to distinguish similar objects and do not represent a specific ordering of the objects.

[0017] In an embodiment of the present invention, a sterilization control method for a bioreactor is provided, which is applied to a bioreactor group, wherein the bioreactor group includes two bioreactors, each of which includes a body and a jacket sleeved on the outside of the body, the body is provided with a first valve and a second valve, the jacket is provided with a third valve and a fourth valve, the two bioreactors are defined as a first bioreactor and a second bioreactor, the second valve of the first bioreactor is connected to the fourth valve of the second bioreactor, and the fourth valve of the first bioreactor is connected to the second valve of the second bioreactor (refer to Figure 1 The second valve and the fourth valve of the first bioreactor are the body outlet valve 1 and the jacket inlet valve 3 of reactor 1, respectively; the second valve and the fourth valve of the second bioreactor are the body outlet valve 2 and the jacket inlet valve 3 of reactor 2, respectively). The jacket provides a sealed space surrounding the body, the inner side of the jacket contacts the outer side of the body, the temperature of the jacket is transmitted to the body, and when the temperature of the jacket rises, the temperature inside the body rises.

[0018] The sterilization control method comprises the following steps:

[0019] Step S110, when the first bioreactor is sterilized and the second bioreactor is fermented, the second valve of the first bioreactor and the fourth valve of the second bioreactor are controlled to be opened, and the fourth valve of the first bioreactor and the second valve of the second bioreactor are controlled to be closed.

[0020] Step S120, when the first bioreactor is undergoing biological fermentation and the second bioreactor is undergoing air sterilization, the fourth valve of the first bioreactor and the second valve of the second bioreactor are controlled to be opened, and the second valve of the first bioreactor and the fourth valve of the second bioreactor are controlled to be closed.

[0021] Specifically, a serial bioreactor system is more common in industry, and it usually includes multiple bioreactors. The present invention connects some valves of two adjacent bioreactors. Specifically, for a single bioreactor, it includes at least four valves, two of which are installed on the kettle body, serving as the air inlet valve and the air outlet valve of the kettle body, respectively, and the other two are installed on the jacket, serving as the air inlet valve and the air outlet valve of the jacket, respectively. Also, when a single bioreactor is sterilized by air, steam is introduced through one valve and discharged through another valve, so that steam is circulated in the bioreactor. And the internal temperature of the kettle body can be adjusted by adjusting the flow rate of the two valves. For example, increasing the flow rate of the air inlet valve or reducing the flow rate of the air outlet valve can increase the internal temperature of the kettle body.

[0022] In step S110, the first bioreactor is sterilized in air, and steam is introduced into the first bioreactor through the first valve and discharged through the second valve. Different from the conventional sterilization in air, the present invention introduces the steam discharged from the first bioreactor into the jacket of the second bioreactor, thereby providing heat for the biological fermentation of the second bioreactor, that is, maintaining the internal temperature of the second bioreactor at a suitable temperature.

[0023] Similarly, in step S120, the second bioreactor is sterilized in an airtight manner, and steam is introduced into the second bioreactor through the first valve and discharged through the second valve. The steam discharged from the second bioreactor is introduced into the jacket of the first bioreactor, thereby providing heat for the biological fermentation of the first bioreactor, that is, maintaining the internal temperature of the first bioreactor at a suitable temperature.

[0024] Correspondingly, in the above process, the fourth valve on the jacket serves as the air inlet valve of the jacket, and the third valve serves as the air outlet valve of the jacket. At this time, the internal temperature of the jacket can be controlled by adjusting the flow of the third valve, thereby adjusting the internal temperature of the kettle.

[0025] In summary, the sterilization control method of the bioreactor provided by the present invention connects some valves of two adjacent bioreactors. When one of the bioreactors is sterilized by air, its excess steam is discharged into the jacket of another bioreactor to provide the heat required for biological fermentation. Compared with the prior art, in which the steam used for air sterilization is directly discharged out of the system, the present invention improves the steam utilization rate, thereby reducing the waste of water resources and thermal resources as a whole, and solves the problem of low resource utilization in the current steam air sterilization method of the reactor.

[0026] In some embodiments, a steam flow meter is provided on the first valve and the second valve of each bioreactor; and a pressure sensor and a distributed temperature sensor are provided in the body of each bioreactor. Figure 2 The first valve and the second valve of the bioreactor are the kettle body air inlet valve 11 and the valve body air outlet valve 1, both of which are provided with a steam flow meter 10, and a pressure sensor 12 is provided on the top wall inside the kettle body.

[0027] Reference Figure 3 , sterilization control methods also include:

[0028] Step S130, for the bioreactor undergoing air sterilization, obtaining the actual steam flow value of the steam flow meter, the actual pressure value of the pressure sensor, and the actual temperature value of the distributed temperature sensor.

[0029] Step S140: when the lowest actual temperature value in the distributed temperature sensors is lower than the target temperature value, the steam flow rate of the first valve is increased and the steam flow rate of the second valve is decreased.

[0030] Step S150: when the lowest actual temperature value in the distributed temperature sensors is higher than the target temperature value, the steam flow rate of the first valve is reduced and the steam flow rate of the second valve is increased.

[0031] Specifically, in the air sterilization process, it is necessary to obtain the actual steam flow value, actual pressure value and actual temperature value of the bioreactor in real time to monitor various indicators. Air sterilization requires the internal temperature of the kettle to be maintained at a target temperature value. For example, in an air sterilization process, the target temperature value is 121°C. The internal temperature of the kettle is mainly achieved by controlling the steam flow rate. Usually, when the incoming steam is greater than the outgoing steam, the internal temperature of the kettle will rise, and when the incoming steam is less than the outgoing steam, the internal temperature of the kettle will drop. Then, the first valve and the second valve can be controlled by this rule to achieve the regulation of the internal temperature of the kettle.

[0032] Furthermore, the sterilization control method also includes:

[0033] Step S160, determining whether the target sterilization condition is maintained for a preset time.

[0034] When the target sterilization conditions are maintained for a preset time, sterilization is terminated; otherwise, the F value of sterilization is calculated, and when the F value meets the target time value, sterilization is terminated; wherein the target sterilization conditions include that the lowest actual temperature value in the distributed temperature sensor is higher than the target temperature value and the actual pressure value of the pressure sensor is maintained at the target pressure value.

[0035] Generally, when the internal temperature of the kettle is always higher than the target temperature value and maintained for a preset time, it is considered that the sterilization is sufficient. Since it is necessary to ensure that every position inside the kettle can be fully sterilized, the target sterilization condition requires that the minimum actual temperature value is higher than the target temperature value. It should be noted that, unless otherwise specified, the internal temperature of the kettle referred to in other places of the present invention is the average temperature of the distributed sensor.

[0036] Furthermore, through step S140 and step S150, the internal temperature of the kettle can generally be maintained above the target temperature value, but it cannot be guaranteed that it can always be maintained at the target temperature value within the preset time. In this case, the sterilization F value can be calculated to determine whether the sterilization is sufficient, and the F value represents the equivalent sterilization time at the preset temperature.

[0037] Exemplarily, in one embodiment, the target temperature value is 121°C, the preset time is 30 minutes, and the F value is F0 value at this time. The F0 value represents the equivalent sterilization time at 121°C, and the preset temperature is 121°C at this time.

[0038] The calculation formula of F0 value is as follows:

[0039] ,

[0040] in, t 1 and t 2 are the start time and end time of sterilization respectively, Z is the sterilization temperature coefficient, T is the internal temperature of the kettle, and the sterilization temperature coefficient can be 10℃.

[0041] The target time value is 12 minutes.

[0042] For the air sterilization process of a certain bioreactor, even if its target sterilization conditions cannot be maintained for the preset time, but its F0 value is greater than 12 minutes, it can be considered that the air sterilization is sufficient.

[0043] It should be noted that the determination of whether the target sterilization conditions are maintained for the preset time and the calculation of the F0 value can be performed in real time. When one of the sterilization end conditions is met, the sterilization can be ended, otherwise the sterilization continues.

[0044] In some of the embodiments, the sterilization control method further includes: performing Kalman filtering on the actual steam flow value; and / or correcting the actual pressure value.

[0045] Taking into account the noise interference of the pressure sensor and the steam flow sensor, after obtaining the actual pressure value and the actual steam flow value, they need to be denoised to improve data accuracy.

[0046] Specifically, the Kalman filter processing of the actual steam flow value includes:

[0047] Establish the steam flow observation equation:

[0048] Z k = F k + v k ,

[0049] in, Z k is the observed value of steam flow at time k, F k is the expected value of steam flow at time k, v k is the measurement noise of the steam flow at time k.

[0050] Make an a priori estimate of the steam flow rate:

[0051] ,

[0052] in, C is the specific heat capacity of water, m is the steam quality in the kettle, is the temperature change per unit time, L is the latent heat of vaporization of water, and They are the prior estimate of the steam flow rate at time k and the posterior estimate at time k-1 respectively.

[0053] Calculate the steam flow covariance:

[0054] ,

[0055] in, is the predicted value of the steam flow covariance at time k, is the posterior estimate of the steam flow covariance at time k-1, is the pair at k-1 time The Jacobian matrix obtained by linearization is w kis the process noise of steam flow at time k, Q is the covariance matrix of process noise, and the superscript T represents the matrix transpose.

[0056] Calculate the steam flow gain factor:

[0057] ,

[0058] in, K k is the gain coefficient at time k, H is the coefficient matrix of the observation equation, v k is the measurement noise at time k, R is the covariance matrix of the measurement noise.

[0059] Calculate the a posteriori estimate of the steam flow rate:

[0060] ,

[0061] in, is the posterior estimate of the steam flow rate at time k, It is the nonlinear expression of the expected value of the steam flow at time k.

[0062] Update the steam flow covariance:

[0063] ,

[0064] in, P k is the posterior estimate of the steam flow covariance at time k, I is the identity matrix, is the predicted value of the steam flow covariance at time k.

[0065] In this embodiment, Kalman filtering is used to process the actual steam flow value, thereby eliminating noise in the data, and further obtaining a more accurate calculation of the steam flow in the two valves.

[0066] The kettle body is composed of a cylinder and two spherical caps. The correction of the actual pressure value includes:

[0067] The theoretical pressure value is calculated according to the ideal gas equation, which is:

[0068] ,

[0069] in, P theory is the theoretical pressure value, V is the volume of the reactor, n and R are the gas constant and molar number of steam, respectively,T is the internal temperature of the kettle, V 1 is the volume of the two spherical caps, V 2 is the volume of the cylinder, r and h are the radius and height of the spherical cap, S and L are the cross-sectional area and length of the cylinder respectively.

[0070] Correct the actual pressure value according to the theoretical pressure value.

[0071] In this embodiment, the theoretical pressure value is calculated based on the ideal gas equation and the internal temperature of the kettle body and the actual volume of the kettle body. When there is a difference between the theoretical pressure value and the actual pressure value, the actual pressure value can be corrected. For example, the theoretical pressure value can be used as the internal pressure of the kettle body, or the theoretical pressure value and the actual pressure value can be summed and averaged as the internal pressure of the kettle body.

[0072] In some of the embodiments, reference Figure 2 The distributed sensor includes a thermometer 8 and multiple wireless probes 5, and the multiple wireless temperature probes 5 are wirelessly connected to the thermometer 8; the bioreactor also includes a temperature measuring installation, and the temperature measuring installation includes a mounting plate 9 and multiple rotating heads 6. The mounting plate 9 is threadedly sleeved on the stirring rotating shaft inside the reactor body, and the multiple rotating heads 6 are evenly installed on the surrounding side of the mounting plate 9, and the multiple wireless temperature probes 5 are respectively installed on the multiple rotating heads 6.

[0073] In the present embodiment, since the mounting plate is threadedly matched with the stirring rotating shaft, the rotation of the stirring rotating shaft can drive the mounting plate to move up and down, thereby adjusting the height of the probe. The above is achieved by utilizing the inertia of the mounting plate. For example, in a stationary state, the stirring rotating shaft suddenly accelerates and rotates. In the process of accelerated rotation, the mounting plate is moved a certain distance along the axial direction of the stirring rotating shaft by thread matching. Under the uniform rotation state, since there is a certain friction force in the thread matching, the mounting plate and the stirring rotating shaft can rotate synchronously. Therefore, during the fermentation process, the mounting plate does not need to be disassembled, and the mounting plate can play a stirring role. At the same time, the rotating head can rotate within a large angle range, thereby adjusting the direction of the probe. Specifically, the rotating head can adopt an electric direction adjustment mechanism, such as a structure for adjusting the direction of the camera in a camera. Therefore, through the mounting plate and the rotating head, the probe can perform temperature detection on each position inside the kettle.

[0074] As follows, the sterilization control method of the bioreactor in the present invention is further described through a specific embodiment.

[0075] In a specific embodiment, the sterilization control method of the biological reactor has the following characteristics:

[0076] 1. With the remote monitoring operating system, one person can complete the opening and closing of on-site valves and the monitoring of real-time parameters on site. First check whether each valve is completely closed. After confirmation, open the steam generator water inlet valve through the controller, start the steam generator, and the steam produced is sterilized by the air filter before being transported through the pipeline.

[0077] 2. Air sterilization: First, introduce steam into the jacket, and when the internal temperature of the reactor reaches 90 degrees. Pass pure steam through the steam valve for sterilization. When the temperature reaches 121 degrees, the pipeline valves such as the feed valve and the discharge valve are opened and steam is passed (additional steam is passed through the feed valve and the discharge valve to increase the steam inflow), and the temperature is maintained for 30 minutes. By performing Kalman filtering on the steam flow of the steam inlet valve and the outlet valve, more accurate temperature data can be obtained during sterilization. A steam flow meter is set on the side of the steam inlet valve and the outlet valve to monitor the steam flow in real time. When the temperature in the reactor is greater than 121 degrees, reduce the opening of the steam inlet valve and increase the opening of the steam outlet valve. When the temperature in the reactor is less than 121 degrees, increase the opening of the steam inlet valve and reduce the opening of the steam outlet valve.

[0078] When the temperature is higher than 150 degrees, the automatic alarm system of the reactor is triggered, and the alarm information is transmitted to the remote monitoring end through the controller. The operator closes the steam inlet valve at the remote end. If a fault occurs and it cannot be closed, the on-site operator is immediately notified for emergency treatment. The tank pressure is maintained at 0.1Mpa, and the air filter and pipeline are sterilized at the same time. The discharge valve, feed valve and other valves are slightly opened.

[0079] 3. If reactor 1 is in the sterilization process and reactor 2 is in the fermentation process, outlet valve 1 and inlet valve 4 are opened, outlet valve 2 and inlet valve 3 are closed, and excess steam from reactor 1 is introduced into the jacket of reactor 2, and vice versa. Most of the residual heat is transferred through the pipeline to heat the reactor.

[0080] 4. This embodiment does not change the time and temperature required for sterilization, thus maintaining the same sterilization effect as the original process flow. It is an optimization of the original reactor sterilization process. Since the measurement accuracy of the steam flow meter affects the current sterilization temperature, in order to ensure the measurement accuracy, the extended Kalman filter algorithm is used to calibrate and optimize the online monitoring steam flow meter. The prediction equation is established based on the heat balance between the steam entering through the steam inlet valve and the cavity gas in the reactor per unit time:

[0081] Assume that in unit time [ k -1, k ]( k =1,2,3… n ), the heat change per unit time at the steam pipe inlet valve isQ 1k = Q 2k .

[0082] Q 1k Produces steam heat for heaters, Q 2k is the heat of the air change in the kettle body, and the heat dissipated by the kettle body itself can be ignored. Then:

[0083] Q 1k = FL

[0084] F is the steam mass entering the kettle measured by the gas flow meter per unit time, L is the latent heat of vaporization of water.

[0085]

[0086] C is the specific heat capacity of water, m is the steam quality in the kettle, is the temperature change per unit time. Based on this, the prediction equation is established:

[0087] ,

[0088] Establishing the steam flow observation equation Z k :

[0089] Z k = F k + v k ;

[0090] in, F k For the current moment t k The expected value of steam flow, v k For the current moment t k Measurement noise of steam flow.

[0091] Make an a priori estimate of the steam flow rate:

[0092] ;

[0093] The influence of noise is not considered when performing a priori estimation. w is 0 and therefore is not reflected in the a priori estimate calculation.

[0094] Calculate the steam flow covariance:

[0095] ;

[0096] in, For the current moment t k Predicted value of steam flow covariance; For the previous moment t k-1 A posteriori estimates of the steam flow rate covariance; For the previous moment t k-1 The Jacobian matrix obtained by linearizing the posterior estimate.

[0097] To extend the Kalman filter process noise, w k It is the current moment t k The process noise, Q is the covariance matrix of the process noise.

[0098] Calculate the steam flow gain factor:

[0099] ;

[0100] in, K k For the current moment t k The gain factor, H The observation equation Z k The coefficient matrix of is the measurement noise of the extended Kalman filter, v k is the current step measurement noise, R is the covariance matrix of the measurement noise.

[0101] Calculate the a posteriori estimate of the steam flow rate:

[0102] ;

[0103] in, For the current moment t k The a posteriori estimate of the steam flow rate, That is, a nonlinear expression for the expected value of steam flow.

[0104] Update the steam flow covariance:

[0105] ;

[0106] in, P k For the current moment t k The a posteriori estimate of the steam flow rate covariance, I is the identity matrix.

[0107] 5. In a high temperature environment, due to the influence of heat radiation and heat conduction, the temperature distribution at the edge of the reactor often presents discontinuous or sudden changes. The temperature changes inside the reactor can be monitored in real time and accurately through distributed fiber optic temperature sensors. According to the actual situation on site, a point fiber optic temperature measurement system can be used because it can accurately measure at a specific point. Evenly distributed on the stirring blades, the angle can be rotated at will to meet the temperature detection of any corner of the sterilization process inside the reactor, avoiding bacterial contamination caused by incomplete sterilization and inadequate monitoring.

[0108] During sterilization, the high-temperature water vapor introduced can be regarded as an ideal gas. The pressure sensor is affected by the complex environment in the autoclave during long-term use, and the internal components of the sensor are subject to wear and aging, and the accuracy will gradually deteriorate, resulting in a deviation between its output signal and the actual pressure value.

[0109] So record the current pressure sensor reading P Sensor , according to the ideal gas equation:

[0110] PV = nRT

[0111] Substitute the known V , T and n (moles of gas), n , R are the gas constant and molar number of steam, V is the current gas volume in the kettle, T is the current gas temperature. Through calculation, it is known that: the main body of the kettle is a cylindrical structure, and a kettle top and a kettle bottom with a spherical crown structure are arranged above and below the main body of the kettle.

[0112] V It can be regarded as the sum of the volumes of a cylinder plus two spherical caps as shown in the figure, from which we can find: V = V 1+ V 2, among which, V 1 is the volume of the two spherical caps, V 2 is the volume of the cylinder.

[0113] According to the volume calculation formula of the spherical cap, the volume of gas that can be accommodated by the curved surface of the spherical cap is:

[0114] ;

[0115] in, r is the radius of the sphere that intercepts the spherical cap; h is the height of the spherical crown.

[0116] ;

[0117] in, S is the cross-sectional area of ​​the cylinder, L is the length of the cylinder inside the reactor. If the reactor body is of other shapes, the corresponding shape calculation formula needs to be used to express the gas volume above the reactor.

[0118] The theoretical pressure value can be calculated using the ideal gas equation P theory , through the correction factor k Correct the current pressure sensor value, the expression is:

[0119]

[0120] This correction factor k Reflects the deviation ratio between the sensor reading and the theoretical value. k If greater than 1, the sensor reading is low; k If the value is less than 1, the sensor reading is too high. Multiply the sensor reading by the correction factor to get a value closer to the actual pressure.

[0121] 6. As a device capable of high temperature and high pressure wet heat sterilization, the sterilization process of the reactor can be evaluated using the F0 value formula.

[0122]

[0123] The F0 value is defined as: F0 converts the different heating temperatures and times of the sterilized items during the sterilization process to a sterilization time equivalent to the thermal efficiency of hot press sterilization at 121°C. T is the current temperature inside the reactor, Z is the sterilization temperature coefficient.

[0124] It should be noted that the Z value is not fixed, it depends on factors such as the specific type of microorganism, environmental conditions, and sterilization process. Therefore, in practical applications, the appropriate Z value should be selected for calculation and analysis according to the specific situation.

[0125] In this way, during the sterilization process, as long as the temperature and time of the sterilized items are recorded, the F0 value can be calculated through the formula. This can ensure that the sterilization process achieves the predetermined sterilization effect and ensures the quality and safety of the product. In order to ensure the full sterilization of the reactor, F0 is taken as 12 points here.

[0126] In addition, for different types of reactors and sterilization processes, the F0 value formula needs to be appropriately adjusted and optimized.

[0127] Reference Figure 2 The wireless temperature probe 5 can rotate 180° up and down around the rotating head 6 to fully illuminate every pipe connection of the reactor. The outer side of the stirring shaft adopts a spiral rise and fall to adjust the position of the temperature probe.

[0128] In summary, the sterilization control method of the present invention can prevent the waste of a large amount of water resources and thermal resources, is economical and environmentally friendly, and can improve production efficiency. The accuracy of important measuring instruments in the sterilization process can be improved, and the purpose of temperature measurement can be achieved at any position in the internal space of the kettle. Different evaluation indicators can be adopted to save production time and avoid the time cost caused by restarting sterilization.

[0129] The present invention also provides a method for sterilizing a bioreactor, and the sterilization control method for the bioreactor provided by the present invention is used for sterilization control. Specifically, the sterilization control method can be used to control the opening and closing of corresponding valves and the flow rate.

[0130] The present invention also provides a sterilization control device for a bioreactor, which is applied to a bioreactor group. The bioreactor group includes two bioreactors, each of which includes a body and a jacket sleeved on the outside of the body, the body is provided with a first valve and a second valve, the jacket is provided with a third valve and a fourth valve, the two bioreactors are defined as a first bioreactor and a second bioreactor, the second valve of the first bioreactor is connected to the fourth valve of the second bioreactor, and the fourth valve of the first bioreactor is connected to the second valve of the second bioreactor;

[0131] The sterilization control device comprises:

[0132] A first control module is used for controlling the second valve of the first bioreactor and the fourth valve of the second bioreactor to open, and controlling the fourth valve of the first bioreactor and the second valve of the second bioreactor to close when the first bioreactor is sterilized and the second bioreactor is fermented;

[0133] The second control module is used to control the fourth valve of the first bioreactor and the second valve of the second bioreactor to open, and control the second valve of the first bioreactor and the fourth valve of the second bioreactor to close when the first bioreactor is performing biological fermentation and the second bioreactor is performing air sterilization.

[0134] The sterilization control device of the bioreactor provided by the present invention connects some valves of two adjacent bioreactors. When one of the bioreactors is sterilized by air, its excess steam is discharged into the jacket of the other bioreactor to provide the heat required for biological fermentation. Compared with the prior art, in which the steam used for air sterilization is directly discharged out of the system, the present invention improves the steam utilization rate, thereby reducing the waste of water resources and thermal resources as a whole, and solves the problem of low resource utilization in the current steam air sterilization method of the reactor.

[0135] It should be understood that the specific embodiments described here are only used to explain this application, rather than to limit it. According to the embodiments provided in this application, all other embodiments obtained by ordinary technicians in this field without creative work are within the protection scope of this application.

[0136] Obviously, the drawings are only some examples or embodiments of the present application. For ordinary technicians in the field, the present application can also be applied to other similar situations based on these drawings without creative work. In addition, it is understandable that although the work done in this development process may be complicated and lengthy, for ordinary technicians in the field, certain changes in design, manufacturing or production based on the technical content disclosed in this application are only conventional technical means and should not be regarded as insufficient content disclosed in this application.

Claims

1. A sterilization control method for a bioreactor, applied to a bioreactor group, wherein the bioreactor group comprises two bioreactors, each of which comprises a body and a jacket sleeved on the outside of the body, the body is provided with a first valve and a second valve, the jacket is provided with a third valve and a fourth valve, the two bioreactors are defined as a first bioreactor and a second bioreactor, and characterized in that: The second valve of the first bioreactor is connected to the fourth valve of the second bioreactor, and the fourth valve of the first bioreactor is connected to the second valve of the second bioreactor; a steam flow meter is provided on the first valve and the second valve of each bioreactor; a pressure sensor and a distributed temperature sensor are provided in the body of each bioreactor; The sterilization control method comprises: When the first bioreactor is sterilized and the second bioreactor is fermented, the second valve of the first bioreactor and the fourth valve of the second bioreactor are controlled to be opened, and the fourth valve of the first bioreactor and the second valve of the second bioreactor are controlled to be closed; When the first bioreactor is undergoing biological fermentation and the second bioreactor is undergoing air sterilization, the fourth valve of the first bioreactor and the second valve of the second bioreactor are controlled to be opened, and the second valve of the first bioreactor and the fourth valve of the second bioreactor are controlled to be closed; For a biological reactor that is undergoing air sterilization, an actual steam flow value of the steam flow meter, an actual pressure value of the pressure sensor, and an actual temperature value of the distributed temperature sensor are obtained, and the actual pressure value is corrected; When the lowest actual temperature value in the distributed temperature sensor is lower than the target temperature value, increasing the steam flow rate of the first valve and reducing the steam flow rate of the second valve; When the lowest actual temperature value in the distributed temperature sensor is higher than the target temperature value, reducing the steam flow rate of the first valve and increasing the steam flow rate of the second valve; When the target sterilization condition is maintained for a preset time, the sterilization is terminated; otherwise, the F value of the sterilization is calculated, and when the F value meets the target time value, the sterilization is terminated; the F value represents the equivalent sterilization time at the preset temperature; The target sterilization condition includes that the lowest actual temperature value in the distributed temperature sensor is higher than the target temperature value and the actual pressure value of the pressure sensor is maintained at the target pressure value; and the kettle body is composed of a cylinder and two spherical caps, and the actual pressure value is corrected including: The theoretical pressure value is calculated according to the ideal gas equation, which is: in, P theory is the theoretical pressure value, V is the volume of the reactor, n and R are the gas constant and molar number of steam, respectively, T is the internal temperature of the kettle, V 1 is the volume of the two spherical caps, V 2 is the volume of the cylinder, r and h are the radius and height of the spherical cap, S and L are the cross-sectional area and length of the cylinder respectively; The actual pressure value is corrected according to the theoretical pressure value.

2. The sterilization control method of a biological reactor according to claim 1, characterized in that: The target temperature value is 121° C., the preset time is 30 min, and the F value is the F0 value, which represents the equivalent sterilization time at 121° C.

3. The sterilization control method of a biological reactor according to claim 2, characterized in that: The calculation formula of the F0 value is as follows: in, t 1 and t 2 are the start time and end time of sterilization respectively, Z is the sterilization temperature coefficient, T is the internal temperature of the kettle; The target time value is 12 minutes.

4. The sterilization control method of a biological reactor according to claim 1, characterized in that: The sterilization control method also includes: The actual steam flow value is subjected to Kalman filtering processing.

5. The sterilization control method of a biological reactor according to claim 4, characterized in that: Performing Kalman filtering on the actual steam flow value includes: Establish the steam flow observation equation: in, Z k is the observed value of steam flow at time k, F k is the expected value of steam flow at time k, v k is the measurement noise of steam flow at time k; Make an a priori estimate of the steam flow rate: in, C is the specific heat capacity of water, m is the steam quality in the kettle, is the temperature change per unit time, L is the latent heat of vaporization of water, and are the prior estimate of the steam flow rate at time k and the posterior estimate at time k-1 respectively; Calculate the steam flow covariance: in, is the predicted value of the steam flow covariance at time k, is the posterior estimate of the steam flow covariance at time k-1, is the pair at k-1 time The Jacobian matrix obtained by linearization is is the process noise of steam flow at time k, Q is the covariance matrix of process noise, and the superscript T indicates matrix transpose; Calculate the steam flow gain factor: in, K k is the gain coefficient at time k, H is the coefficient matrix of the observation equation, v k is the measurement noise at time k, R is the covariance matrix of the measurement noise; Calculate the a posteriori estimate of the steam flow rate: in, is the posterior estimate of the steam flow rate at time k, is the nonlinear expression of the expected value of the steam flow at time k; Update the steam flow covariance: in, is the posterior estimate of the steam flow covariance at time k, I is the identity matrix, is the predicted value of the steam flow covariance at time k.

6. The sterilization control method of a biological reactor according to claim 1, characterized in that: The distributed sensor includes a thermometer and a plurality of wireless temperature probes, and the plurality of wireless temperature probes are electrically connected to the thermometer; The bioreactor further comprises a temperature measuring installation part, which comprises a mounting plate and a plurality of rotating heads. The mounting plate is threadedly sleeved on the stirring rotating shaft inside the reactor body, the plurality of rotating heads are evenly mounted on the peripheral side of the mounting plate, and the plurality of wireless temperature probes are respectively mounted on the plurality of rotating heads.

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