SU981966A1 - Fermentation periodic process automatic control method - Google Patents

Description

The invention relates to the automatic control of microbial cultivation processes, carried out in several stages in periodically maintained apparatuses, and can be used in the production of pharmaceutical chemistry and microbiological production.

A known method for automatically determining the end of the biosynthesis process, implemented by a device for controlling the concentration of biosynthesis products in periodic microorganism cultivation processes, consists in measuring the concentration of biosynthesis products in a fermenter at equal intervals of time, comparing the current concentration value with the memorized previous value and when the latter value is equal to the current value concentrations are judged to terminate or slow down the process of Cl biosynthesis.

 The disadvantage of this method lies in the fact that achieving the maximum value of the concentration of biosynthesis products in periodic fermentation processes, including the processes of growing microorganisms of several stages of generation

and the actual process of obtaining the target product does not always correspond to the optimal end of each of these processes, which leads to a deterioration in the optimal conditions for carrying out the process of obtaining the target product and, consequently, to a decrease in the yield of the target product and an increase in operating costs.

ten

The closest in technical essence is a method of automatic control of a periodic fermentation process, consisting in controlling temperature, air flow for aeration, pressure in the apparatus of each stage in measuring the biomass concentration at the first and second stages of biomass cultivation and the concentration of the target product,

20 adjusting the acidity of the medium, the concentration of Oxygen dissolved in it at the stage of biosynthesis of the target product and determining the end of the latter, taking into account the concentration of the product and the duration of the process 2.

The disadvantage of this control method is that it does not take into account the effect of the previous microorganism cultivation processes and the subsequent technological stage of production on the implementation and the end of the process of obtaining the target product, which leads to a decrease in the productivity of the process and an increase in running costs. The purpose of the invention is to increase the productivity of the process and reduce costs. The goal is achieved by the method of automatic control of a periodic fermentation process, consisting in controlling the temperature, air flow for aeration, pressure in the apparatus of each stage, measuring the biomass concentration in the first and second stages of biomass cultivation and the concentration of the target product, controlling the acidity of the medium, concentration of oxygen dissolved in it at the stage of biosynthesis of the target product, and determining the end of the latter, taking into account the concentration of the target product product duration and duration, measure the duration of the process of growing biomass in the first stage J is compared with the set value and depending on the result of the comparison and the concentration of biomass B, the device corrects the end of the first stage process, determines the specific rate of biomass growth in the second stage of the process, while the moment of termination of the process of growing biomass in the first flock is set to achieve the maximum value of the biomass concentration at this stage with the process duration not exceeding given at the second stage - with a negative sign of the derivative of the maximum given growth rate of 6Horviaccb7 at this stage and the end of the process of obtaining the target product is carried out according to the maximum value of the ratio of the profit obtained during the fermentation cycle to the duration of the process. the scheme of the automatic control system for the batch fermentation process implementing this method. The system contains circuits for stabilizing temperature, pressure and air flow. To aerate the medium in inoculant 1, seed apparatus 2 and fermenter 3, contours for stabilizing the acidity of the medium in fermenter 3 and controlling the concentration of oxygen dissolved in it; a device for fixing the moment of termination of the process of biomass cultivation in the inoculant, including a concentration sensor 4, a storage unit 5, a comparison block, a timer 7, measuring the efficiency of the process in the inoculator associated with a concentration sensor 4, a threshold element 8, the input of which is connected to the output of the timer 7, and the output to the input of the logic element 9 OR, the output of which is connected to the logic unit 10 connected to the command unit 11. The output of the latter is connected to the actuator 12 installed on the line before The media from inoculum 1 in the inoculum 2 and to the input of the switching relay 13, to another input of which the block 14 is connected, specifies the optimal temperature in the inoculum 1. The temperature stabilization circuit in the inoculum 1 turns on the temperature sensor 15, the output of which is connected to a variable the input of the controller 16, to the driver input of which the output of the optimum temperature setting unit 14 is connected by means of a switching relay 13, the output of the controller 16 is connected to the actuator 17 installed on the cooling supply line boiling water. The stabilization circuit for air flow to aeration consists of a flow sensor 18 connected to the input of the regulator 18, the output of which is connected to the actuator 20 installed on the air supply line to the aeration. The pressure stabilization circuit in inoculator 1 contains a sensor 21 connected to the variable input of the regulator 22, to the output input of which the output of the command unit 11 is connected, the output of the regulator 22 is connected to the actuator 23 installed on the line of the gases coming from the inoculation gas . The device for fixing the moment when the biomass cultivation process ends at the seeding device 2 includes a concentration sensor 24, a concentration change measurement unit 25 connected to the output of sensor 24, a division unit 26, one input of which is connected to the output of concentration sensor 24, and the other input to output unit 25 for measuring the rate of change of concentration, unit 27 for storage, unit 28 for comparison, one input of which is connected to the output of block 26 and the other input is connected to the output of unit 27 for storage, logic unit 29, the input of which is connected chen to the output of comparator unit 28, and an output - to an input command block, -30; the output of the latter is connected to an actuator 31 installed on the medium supply line from the inoculum to the fermentor and to the input of the switching relay 32, another input of which is connected to the unit 33 for setting the optimum, Horo temperature value in the inoculum 2. The temperature stabilization circuit in The seed machine 2 includes a temperature sensor 34, the output of which is connected to the variable input of the regulator 35, to the output input of which the output of the unit 33 for setting the optimum temperature value is connected via a switching relay 3 2, the output of the regulator 35 is connected to an actuator 36 installed on the cooling water supply line. The aeration air flow stabilization loop consists of a flow sensor 37 connected to the controller 38, the output of which is connected to the actuator 39 mounted on the supply line air to aerate. The pressure stabilization circuit in the seeding device 2 contains a sensor 40 connected to the variable input of the regulator 41, to the output input of which the output of the command unit 30 is connected, the output of the regulator 41 is connected to the actuator 42 installed on the line 2 of the gases coming from the seeding device . The device for fixing the moment of the end of the biosynthesis process in the fermenter 3 includes a concentration sensor 43, a timer 44 and a multiplication unit 45 connected to the output of the concentration sensor 43, the first, second and third setpoint shaping blocks 46-48, the first block 49 and the second summation block 50, connected respectively to the outputs of multiplier 45, the first and second setpoint formation units 46-47, and the outputs of timer 44 and the third setpoint generation unit 48, the outputs of the first and second summation units 49-50, are connected to the input of the computing unit 51, employee for determining the ratio of profit to process duration, memory unit 52 and comparison unit 53 connected to computing unit 51, logic unit 54 associated with command block 55, whose output is connected to the inputs of switching relays 56, 57 and 58, to the other inputs of which are connected to blocks 59-61 of setting the optimum temperature profile, the concentration of dissolved oxygen and the acid medium in the fermenter 3. The temperature stabilization circuit in the fermenter includes a temperature sensor 62, the output of which is connected to Nome entry controller 63, to specify which entry by the switching relay 56 connected to the output unit 59 specifying the optimum temperature profile in the fermenter, the output of the regulator 63 is coupled to an actuator 64 mounted on the water supply line ohlazhdgooschey. The stabilization circuit for air flow to aeration consists of a flow sensor 65 connected to a stabilization controller 66, air flow, the controller output is connected to an actuator 67 installed on the air line for aeration, and a corrective circuit including a concentration sensor 68 dissolved oxygen, the output of which is connected to the variable input of the regulator 69, to the reference input of which by means of a switch. Relay 57 is connected to the output of the block 60 setting the optimal concentration of dissolved oxygen, the output of the regulator 69 is connected to the correcting input of the regulator 66. stabilize the air flow. The pH stabilization circuit in the fermenter includes a pH meter sensor 70 connected to a variable input of the regulator 71, to the output input of which, by means of a switching relay 58, the output of the unit 61 for setting the optimum acidity profile of the medium in the fermenter is connected, the output of the regulator 71 is connected to the actuator 72, installed on a-. Research Institute feeds into the fermenter 3 titrants. The pressure stabilization loop in the fermenter 3 contains a pressure sensor 73 connected to the variable input of the regulator 74, to the output input of which the output of the command unit 55 is connected, the output of the regulator 74 is connected to the actuator 75 installed on the gases leaving the fermenter. The system includes an actuator 76 located on the drain line of the culture fluid from the fermenter 3. The system implementing this method of automatically controlling the periodic fermentation process works as follows. Due to a decrease in the amount of nutrients, the growth rate of biomass (e.g. mycelium) in inoculum 1 decreases and at the end of the process becomes close to zero, although the concentration of biomass continues to increase slightly. Since the process of biomass growth in inoculator 1 is initial in the processing line of the fermentation stage, the task in this case is to accumulate the maximum amount of biomass over a certain time. If the biomass concentration increases, the signal from the concentration sensor 4 increases and enters simultaneously into the memory unit 5, the comparison unit 6 and the input of the timer 7, which simultaneously with the start of the biomass concentration measurement is activated. Using the comparison unit 6, the current value of the biomass concentration is compared with the result of the previous concentration value measured at a different point in time. If the current concentration value is greater than the previous one, then at the output of the comparison block b, the signal is zero. If, in this case, the transformed signal is proportional to the current duration of the process, below a predetermined value, set on horn element 8, then at its output the signal is also zero. In this case, the signal from the output of the element 9 OR to the input of the logic unit 10 is not received. The latter makes a conclusion about the inconsistency of the duration of the process in the monkor 1 of the time of its optimal termination. The signal at the output of the command unit 11 is zero and the command signal to the switching relay 13 to the actuator 12 and to the driver input of the controller 22 is not received. In this case, the switching to the setpoint input of the temperature controller 16 of the output signal of the unit 14 for setting the optimum temperature continues, and with the help of actuators 17, 20, 23 stabilization is performed at a given optimal temperature level, air consumption for aeration of pressure in inoculator 1. When the previous concentration value will be equal to or greater than the current value of the biomass concentration or the value of the signal proportional to the duration of the process will exceed the specified value set by the threshold element 8, then the output of the comparison block b or the output of the threshold element 8 generates a signal which, through element 9 OR, is fed to the input of the logic unit 10, which generates a signal that the biomass growth in the inoculator 1 is terminated. unit 10 in this case is fed to the input of the com unit 11, from the output of which a signal is sent to the switching of the relay 13, which stops the switching of the signal from the output of the block 14 to the setting input of the regulator 16 and performs the switching of this task regulators 16, 19, 22 from the output commands Nogo unit 11 to the actuators 17, 20, 23 set to the position corresponding to the end of the process. At the same time, with the HELP actuator 12 installed on the medium supply line from the inoculum 1 to the seed drill 2, the biomass is grown in the seed drill 2. The signal from the concentration sensor 24 in the seed drill 2 is fed simultaneously to the input of the rate change unit 25 concentration and to the first input of dividing unit 26, to the second input of which a signal comes from the output of measuring concentration rate measuring unit 25. The signal is proportional to the specific growth rate from the output of dividing unit 26 to the inputs of memory unit 27, where it is stored to the input of comparator unit 28, where it is compared at certain intervals with the result of the previous value of specific growth rate calculated by measuring the concentration at a different time. . The process of growing mycelium in the seed apparatus 2 precedes the process of biosynthesis of the target product, which takes place in the fermenter. Creation of conditions favorable for intensification of product formation in the fermenter 3, leads to the need to obtain at the previous stage of cultivation, i.e. in the sowing apparatus 2, the maximum number of physiologically active mycelium. The moment of attaining the maximum amount of physiologically active mycelium corresponds to the time of the appearance of a negative sign of the maximum specific growth rate and is the moment of the optimal termination of the process in the sowing apparatus 2. Upon reaching this point, the culture is aging, which in turn leads to a decrease in the number of physiologically active mice. and Moreover, if the current value of the specific growth rate of microorganisms is greater than the previous one, which corresponds to the positive sign of the derivative, then at the output of the comparator unit 28, the signal is zero. In this case, the logic unit 29 concludes that the duration of the process does not correspond to the moment of its optimal termination. The signal at the output of the command unit 30 does not occur and the signal at the switching relay 32, at the setting inputs of the regulators 38 and 41 and at the actuator 31 is not fed. In this case, with the help of the regulators 35, 38 and 41, the temperature, air flow and pressure are stabilized at a given optimal level. As the process proceeds, the maximum specific growth rate slightly increases, or is established permanently, and the operation of the stabilizing circuits of the system continues.

Due to the deteriorating culture development conditions, the growth of the mice cells is slowed down by the end of the growing process. In this case, the current value of the maximum specific growth rate determined is less than the previous value memorized. Reducing the maximum specific speed is equivalent to a negative sign of the result of comparing two successively comparing F1 signals in comparative block 28, at the output of which a discrete signal appears, which enters the input of logic unit 29, which concludes that the derivative has a negative sign of maximum specific growth rate. The output signal of the logic unit 29 is fed to the input of the command relay 32, which stops the switching of the signal from the output of the unit 33 to the driver input of the regulator 35 and the switching of this set by the regulators 35, 38 and 41 and the signal to the actuator 31 from the command output block 30, so that the actuators 36, 39 and 42 are installed in a position corresponding to the end of the process, and the actuator 31 transfers the seed biomass from the seed apparatus 2 to the fermenter 3.

The concentration value of the target product, measured in the fermenter 3 by the sensor 43, is fed to the input of the multiplication unit 45, where it is multiplied by a coefficient taking into account the degree of filling of the apparatus.

Simultaneously with the start of the biosynthesis process, a timer 44 is started, changing the duration of the biosynthesis process in the fermenter. Signals proportional to the duration of the process, and a signal proportional to the preparation time of the fermenter 3 to work, coming from the output of the setpoint formation unit 48, are fed to the input of the summing unit 50, the output signal of which is proportional to the total time of the fermentation cycle, is fed to one of the inputs of the computational block 51, to another input of which a signal is output from the summation block 49. The inputs of summation unit 49 receive a signal proportional to the amount of the target product, from the output of multiplication unit 45 and a signal proportional to the loss of the desired product at subsequent stages of the technological process, from the output of the setpoint shaping unit 46, and a signal that takes into account the costs of output | the second block 47 formation; settings. The incoming signals are algebraically summed up in block 49 of summation, and the output signal of this block, proportional to the amount of profit, is fed to the input of the computing unit 51. The signal from the output of the latter is fed to the input of the block

52 memorization, where it is memorized, and to the input of comparator block 53, where

0 is compared to the result of a previous calculation performed on the measured concentration at a different point in time of the fermentation process. IF the current value of the ratio is greater than the previous one, then the output

5 of block 53, the signal is zero. In this case, the logic unit 54 concludes that the duration of the biosynthesis process does not correspond to the time of its optimal completion. The signal at the output of the command block 55 is zero and the signal

the switching relay 56, 57, 58 is not received. The latter continue switching the output signal of blocks 59, 60 and 91 to the control inputs of the regulators, which, using actuators 64, 67 and 72, maintain the temperature, the concentration of dissolved oxygen and the acidity of the medium in the fermenter 3

0 at the optimal level.

When the previous value of the ratio is equal to or greater than the current value of the ratio at the output of the block 51, then the output of the block

five

53 comparison, a signal arrives at the input of a logic unit.

54, which concludes that the maximum value of the ratio has been reached.

0

Logic block output

54 enters the input of the command block 55, which generates a signal for switching relays 56, 57 and 58, which

5 in this case, the switching of the signal from the output of the blocks 59, 60 and 61 to the setting inputs of the regulators 63, 69, 71 is stopped and the switching of this task to the regulators 63, 69, 71 and 74 from the output of the command unit

0

55 so that the actuators 64, 67, 72, 75 are installed at a position corresponding to the end of the process. For example, with the help of the actuator 64, the cooling water supply is stopped, with the help of the actuator 67 the air supply to the aeration is stopped, with the help of the actuator 71 the supply is stopped

0 of the medium regulating the acidity of the culture fluid in the fermenter 3, and using the actuator 75, the apparatus is locked from the environment.

5 When this signal from the output of block 55

an actuator 76 of the olive culture liquid from the fermenter 3 is turned on.

Using this method of automatic control of the periodic fermentation process will increase the productivity of the process by 2% and reduce operating costs.

Claims (2)

1. Author's certificate of the USSR f 467099, cl. C 12 M 1/36, 1975. 2. USSR author's certificate cl. G 05 D 27/00, 1979. №819800 Hamtpuofl