A method for manufacturing a reduced model fermentation tank based on KLA and a fermentation tank

Abstract

The present invention relates to a method for manufacturing a reduced model fermentation tank based on Kla and the fermentation tank. The manufacturing method mainly includes: measuring and obtaining the Kla of a large-scale fermentation tank; using a database to mine the mechanical structure of the reduced model of the large-scale fermentation tank, and finding the mechanical structure of the reduced model that is closest to the Kla of the large-scale fermentation tank; manufacturing the reduced model fermentation tank according to the obtained mechanical structure of the reduced model; wherein the mechanical structure of the reduced model includes: a turbine air collecting plate, a stirring aeration impeller, and a stirring shaft. The Kla of the reduced model is improved by the turbine air collecting plate, the stirring aeration impeller, and the stirring shaft, and the maximum Kla of the reduced model can be kept consistent with the maximum Kla of the production-scale fermentation tank.

Description

Technical Field

[0001] The invention relates to the technical field of bioreactors, and in particular to a method for manufacturing a Kla-based reduced model fermenter and a fermenter. Background Art

[0002] In the fermentation field, production-scale fermenters need to explore the most suitable operating parameters in daily work. However, in the parameter optimization process, due to the large size of production-scale fermenters, the cost of each parameter exploration is very high. It is often time-consuming and labor-intensive to use production-scale fermenters to explore the best operating parameters.

[0003] The existing technology is to use a geometrically similar scaled-down fermenter to optimize the process parameters, and then apply it to a large-scale fermenter.

[0004] Geometric similarity means that the same type of agitator is used on the scaled-down fermenter, and the dimensions of the tank (such as height-to-diameter ratio, baffle size, etc.) are kept proportionally. Although geometrically similar scaled-down model fermenters are considered to represent the production of large-scale fermenters based on existing experience, the relevant parameters can be scaled up and down by linear calculation. However, there is a big difference in Kla performance between small-scale and large-scale fermenters, which often results in that the product quality and process control performance of large-scale fermenters are very different from those of small-scale ones, so it is difficult to evaluate large-scale production processes through geometrically similar scaled-down models.

[0005] In geometrically similar fermenters, the larger the fermentation scale, the larger the Kla. The amount of ventilation during the fermentation process has a great impact on the control of foam, the head space reservation in the tank and the optimization of the process. Since the maximum Kla that can be achieved in large-scale fermenters is larger, the maximum Kla of the reduced model fermenter needs to be increased. Optimizing other process parameters based on similar gas consumption will also better represent the situation of large-scale fermenters.

[0006] To address the above problems, no effective solutions have been proposed yet. Summary of the invention

[0007] Based on this, it is necessary to provide a method for making a reduced model fermentation tank based on Kla and a fermentation tank to address the above technical problems.

[0008] In one aspect, the present invention provides a method for making a scaled-down model fermenter based on Kla, comprising the following steps:

[0009] Step 1: Measure and obtain the Kla of large-scale fermentation tanks under different process parameters;

[0010] Step 2: Use the database to mine the mechanical structure of the scaled-down model of the large-scale fermentation tank, and find the mechanical structure of the scaled-down model that is closest to the Kla of the large-scale fermentation tank under the same process parameters;

[0011] Step 3: manufacturing a reduced model fermentation tank according to the obtained mechanical structure of the reduced model;

[0012] The mechanical structure comprises: a turbine air collecting plate, a stirring aeration impeller and a stirring shaft.

[0013] In some embodiments, the step also includes: performing an actual Kla test on the manufactured scaled-down model fermenter, and improving the scaled-down model until the test results are satisfactory.

[0014] In some embodiments, the Kla of the large-scale fermentor comprises the maximum Kla of the large-scale fermentor.

[0015] In some embodiments, the process parameters include: specific input power P / V, and ventilation volume vvm.

[0016] In some embodiments, the stirring shaft is disposed in the tank body of the reduced model fermentation tank; the stirring shaft is provided with an axially extending first fluid channel, and the stirring shaft is provided with a fluid inlet connected with the first fluid channel;

[0017] The turbine air collecting plate comprises a shell and a guide vane, the shell is sleeved on the outside of the stirring shaft, the diameter of the shell gradually decreases along a first direction, the first direction is parallel to the axial direction of the stirring shaft, one side of the guide vane is connected to the stirring shaft, and the other side is connected to the shell, the guide vane is spirally arranged along the first direction, the guide vane, the stirring shaft, and the shell are enclosed to form a guide channel, the guide channel is connected to the fluid inlet, and one end of the shell away from the bottom of the tank body is set to be an opening and is always located above the working liquid level in the tank body;

[0018] The stirring and aerating impeller is installed at one end of the stirring shaft close to the bottom of the fermentation tank. The stirring and aerating impeller includes a plurality of blades. A second fluid channel connected to the first fluid channel is opened on the blades. The outlet of the second fluid channel is arranged on the side of the blade opposite to the forward rotation direction of the stirring and aerating impeller. The opening direction of the outlet of the second fluid channel is the tangential direction of the stirring and aerating impeller.

[0019] In some embodiments, the first direction is a direction from the top to the bottom of the fermenter.

[0020] In some embodiments, the database is established through the correspondence between the mechanical structures accumulated in actual production and Kla.

[0021] In some embodiments, the actual Kla test is performed on the manufactured scaled-down model fermenter, and the scaled-down model is improved until the test result is satisfactory, including: performing an actual Kla test on the manufactured scaled-down model fermenter, and if the test result meets the Kla deviation requirement with the large-scale fermenter under the same process parameters, the test is terminated; if not, the cause is found and corrected until the deviation requirement is met.

[0022] In some embodiments, the mechanical structure further includes: the height-to-diameter ratio of the tank, the head space in the tank, the number of baffles, and the size of the baffles.

[0023] In another aspect, the present invention also provides a fermentation tank prepared by any of the above methods.

[0024] By implementing the above solution of the present invention, the following beneficial effects can be obtained:

[0025] 1. Through the special stirring structure (turbine gas collecting plate, stirring aeration impeller, stirring shaft), the Kla of the scaled-down model is improved, so that the scaled-down model fermenter and the production-scale fermenter can obtain the same Kla while maintaining the same process parameters, and the maximum Kla of the scaled-down model can be kept consistent with the maximum Kla of the production-scale fermenter. Therefore, the purpose of large-scale fermenter process optimization can be achieved by optimizing the process on the scaled-down fermenter with similar Kla performance, improving the efficiency of the production-scale fermenter process optimization and saving costs.

[0026] 2. Since the operating parameters of the reduced model and the operating parameters of the production scale correspond based on the principle of maximum Kla similarity, it can be easily enlarged to the production scale to improve the efficiency of industrialization.

[0027] 3. It can be used as a satellite fermentation tank for production-scale fermentation tanks. It can "monitor" large-scale production in real time. When there are some quality deviations in the products of large-scale fermentation tanks, the production results and processes of the satellite tanks can be used to find the reasons. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is a schematic diagram of a reduced model fermentation tank of the present invention;

[0029] Figure 2 It is a schematic diagram of the connection relationship between the turbine gas collecting plate and the stirring shaft in the reduced model fermentation tank of the present invention;

[0030] Figure 3 It is a schematic diagram of the connection relationship between the stirring aeration impeller and the stirring shaft in the reduced model fermentation tank of the present invention;

[0031] Figure 4 The figure is a schematic diagram of the connection relationship between the stirring aeration impeller and the stirring shaft in another form of the present invention.

[0032] Description of reference numerals:

[0033] Tank body 1, temperature control unit 2, feeding system 3, air intake system 4, exhaust system 5, stirring system 6, stirring shaft 61, first fluid channel 611, fluid inlet 612, turbine air collecting plate 62, shell 621, guide vane 622, first guide vane 6221, second guide vane 6222, guide channel 623, stirring and aeration impeller 63, blades 631, second fluid channel 632, sampling system 7. DETAILED DESCRIPTION

[0034] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0035] In some embodiments, the present invention provides a method for making a reduced model fermentation tank based on Kla, which is made by the following steps:

[0036] Step 1: Measure the Kla of a large-scale fermenter under different process parameters.

[0037] The Kla of a large-scale fermentation tank is tested using the exhaust method. The exhaust method monitors the change in O2 concentration in the fermentation tank through a dissolved oxygen electrode to obtain the actual Kla value (including the maximum Kla value) at different speeds (including the maximum speed) and different ventilation volumes (including the maximum ventilation volume). The specific steps include: first calibrating the dissolved oxygen electrode, then introducing N2 to remove the O2 in the fermentation tank, and then setting the corresponding parameters according to the speed and ventilation volume designed in the plan. Then, based on the curve of the change of dissolved oxygen value over time recorded by the dissolved oxygen electrode, the slope is calculated to obtain the measured Kla. In addition, by modeling the test results, the corresponding Kla under all operating parameters can be obtained.

[0038] Step 2: Build a database through the relationship between Kla and different mechanical structures.

[0039] In order to solve the problem that the maximum Kla of the reduced model cannot reach the maximum Kla of the large-scale fermentation tank, and the Kla of the reduced model is less than the Kla of the large-scale fermentation tank under the same input power and ventilation volume, the present invention has developed a mechanical mechanism for reducing the scale. It is found that the Kla of the reduced-scale fermentation tank is improved by the mutual cooperation of the turbine gas collecting disk, the stirring aeration impeller, and the stirring shaft, so that its maximum Kla can reach the level of the maximum Kla of the large-scale fermentation tank, and the Kla can be consistent with the Kla of the large-scale fermentation tank under the same process parameters (input power and ventilation volume). The Kla of the fermentation tank formed by the turbine gas collecting disk, the stirring aeration impeller, and the stirring shaft of different sizes and positions is measured and modeled, and the relevant data obtained and the specific structures such as the height-to-diameter ratio of the tank body, the top space in the tank, the number of baffles, the size of the baffles, and the original data of the fermentation tank Kla are obtained by using a computer model-assisted method to obtain the relationship between the above various mechanical structures and Kla, and form a database for subsequent use.

[0040] Step 3: Use the database to mine the mechanical structure of the scaled-down model of the large-scale fermentation tank and find the mechanical structure of the scaled-down model that is closest to Kla of the large-scale fermentation tank.

[0041] According to the Kla performance of the large-scale fermentation tank, the mechanical structure of the reduced model is explored, especially the size of the turbine air collecting plate and the size of the stirring aeration impeller, to find the mechanical structure of the reduced model that is closest to the Kla of the large-scale fermentation tank under the same process parameters.

[0042] Step 4: According to the mechanical structure of the obtained reduced model, a reduced model fermentation tank is manufactured.

[0043] The structure of the scaled-down model fermenter obtained by manufacturing, e.g. Figure 1-4 As shown, a scaled-down model fermentation tank including a turbine air collecting plate, a stirring aeration impeller and a stirring shaft comprises: a tank body 1, a temperature control unit 2, a feeding system 3, an air intake system 4, an exhaust system 5, a stirring system 6 and a sampling system 7, wherein the stirring system 6 comprises a stirring shaft 61, a turbine air collecting plate 62 and a stirring aeration impeller 63.

[0044] The stirring shaft 61 is arranged in the tank body 1, and the axial direction of the stirring shaft 61 is the same as the depth direction of the tank body 1 (the extension direction of the side wall of the tank body 1), and an axially extending first fluid channel 611 is provided on the stirring shaft 61. The stirring shaft 61 is provided with a fluid inlet 612 connected to the first fluid channel 611 (in this embodiment, this is achieved by setting the stirring shaft 61 as a hollow shaft).

[0045] The turbine gas collecting plate 62 includes a shell 621 and a guide vane 622. The shell 621 is sleeved on the outside of the stirring shaft 61. The diameter of the shell 621 is along the first direction ( Figure 1The X direction shown in the figure (i.e., the direction from top to bottom) gradually decreases, that is, the shell 621 is in a truncated cone shape with a larger top and a smaller bottom. The first direction is parallel to the axial direction of the stirring shaft 61. One side of the guide plate 622 is connected to the stirring shaft 61, and the other side is connected to the shell 621. The guide plate is spirally arranged along the first direction. The guide plate, the stirring shaft 61, and the shell 621 are surrounded to form a guide channel 623. The guide channel 623 is connected to the fluid inlet 612. The end of the shell 621 away from the bottom of the tank body 1 ( Figure 2 The upper end of the turbine gas collecting plate 62 is set to an opening and is configured to be always located above the working liquid level in the tank body 1 to ensure that the turbine gas collecting plate 62 can always collect the gas and bubbles above the working liquid level.

[0046] The stirring and aerating impeller 63 has both stirring and aerating functions, and is installed at one end of the stirring shaft 61 close to the bottom of the fermentation tank. The stirring and aerating impeller 63 includes a plurality of blades 631, and a second fluid channel 632 connected to the first fluid channel 611 is opened on the blade 631. The outlet of the second fluid channel 632 is arranged on the side of the blade 631 opposite to the forward rotation direction of the stirring and aerating impeller 63, and the opening direction of the outlet of the second fluid channel 632 is the tangential direction of the stirring and aerating impeller 63.

[0047] The turbine air collecting plate 62 rotates with the stirring shaft 61 and can absorb the surrounding gas or foam. When rotating clockwise, the surrounding gas and foam will be sucked into the guide channel 623 and enter the first fluid channel 611 in the stirring shaft 61 through the fluid inlet 612. When it is reversed counterclockwise, an outward centrifugal force will be generated, which can suck up the liquid of the lower stirring and aeration impeller 63 to achieve the purpose of cleaning the channel and the inside of the impeller. Since a negative pressure will be generated on the back of the blade 631 when the stirring and aeration impeller 63 rotates forward, the gas and foam in the first guide channel 623 can be drawn out through the second guide channel 623. On the other hand, since the forward rotation of the stirring and aeration impeller 63 will also generate centrifugal force, the gas and foam in the first guide channel can also be thrown out by the action of centrifugal force. Among them, the end of the shell 621 close to the bottom of the tank body 1 is set to be closed. And the shell 621 is coaxially arranged with the stirring shaft 61. The guide vane 622 includes a first guide vane 6221 and a second guide vane 6222, and the first guide vane 6221 and the second guide vane 6222 are staggered and spirally arranged along the first direction. The number of fluid inlets 612 is multiple and evenly distributed along the circumference of the stirring shaft 61. The above structure can improve the efficiency of the turbine air collecting plate 62 to absorb the surrounding gas or foam and send it into the first guide channel 623 in the stirring shaft 61. The number of blades 631 is 6 and evenly distributed. The blade 631 is straight plate-shaped or C-shaped arc-shaped, and the direction of the arc-shaped opening is the forward rotation direction of the stirring and aeration impeller 63. The straight plate-shaped blade 631 has a simple structure and is easy to install; while the C-shaped arc-shaped blade 631 has the advantage of being able to further improve the efficiency of stirring and aeration.

[0048] The present invention can aerate at medium and low speeds and under the premise of low shear force requirements by cooperating with the stirring aeration impeller 63, the turbine air collecting plate 62 and the stirring shaft 61, so that the upper gas is dispersed into the solution, thereby improving the Kla of the reduced model fermentation tank, so that the Kla of the reduced model fermentation tank is consistent with that of the large-scale fermentation tank under the same process parameters, and the maximum Kla of the reduced model fermentation tank can reach the same level as the maximum Kla of the large-scale fermentation tank.

[0049] Step 5: Conduct actual Kla test on the manufactured scaled-down model fermenter and improve the scaled-down model until the test results are satisfactory.

[0050] Actual measurements of Kla (including maximum Kla) are performed on the manufactured scaled-down model fermenter. If the deviation of the result from the Kla (including maximum Kla) of the large-scale fermenter meets the requirements, the test is terminated and the possible causes of the deviation need to be found (including inaccurate mechanical structure mined from the database, manufacturing process errors, etc.), and then improvements are made until the purpose of representing the Kla (including maximum Kla) of the large-scale fermenter is achieved.

[0051] Example 1

[0052] Actual measurements were performed on a 10000 L fermenter, a conventionally configured 10 L fermenter, and a 10 L fermenter of the present invention.

[0053] Among them, the 10000L fermenter adopts a three-layer impeller design; the conventional configuration 10L fermenter is a 10L fermenter obtained by proportionally reducing the components of the 10000L fermenter through the principle of geometric similarity; the 10L fermenter of the present invention is a 10L fermenter obtained by the preparation method of the Kla-based reduced model fermenter of the present invention, and the bottom layer of the three-layer impeller adopts the above-mentioned stirring and aeration impeller design, and the above-mentioned turbine air collecting plate and stirring shaft (hollow shaft) are provided.

[0054] The test results are shown in Table 1.

[0055] Table 1

[0056]

[0057] It can be seen that under the conditions of the same specific input power and ventilation volume, the Kla of the conventionally configured 10L fermenter is much smaller than that of the 10000L fermenter, while the 10L fermenter of the present invention can obtain a Kla substantially equal to that of the 10000L fermenter.

[0058] Example 2

[0059] The same fermenter as in Example 1 was used and the equipment parameters were adjusted to obtain the parameters with the maximum Kla for testing.

[0060] The test results are shown in Table 2.

[0061] Table 2

[0062]

[0063] It can be seen that after adjusting the equipment parameters to obtain the maximum Kla of the equipment, the 10L fermenter of the present invention can obtain a maximum Kla that is substantially equal to that of the 10000L fermenter, while the maximum Kla of the conventionally configured 10L fermenter is much smaller than that of the 10000L fermenter.

[0064] The above examples show that the method described in the present invention can obtain a reduced model fermenter with a maximum Kla similar to that of a large-scale fermenter, and the Kla of the reduced model fermenter obtained by the present invention can be consistent with that of the large-scale fermenter under the same process parameters, and there is no problem that the Kla of the fermenter obtained by geometric similarity reduction is much smaller than that of the large-scale fermenter. Therefore, the relevant process parameters of the reduced model fermenter obtained by the present invention can be easily transferred to the large-scale fermenter.

[0065] So far, the embodiments of the present invention have been described in detail. In order to avoid obscuring the concept of the present invention, some details known in the art are not described. Based on the above description, those skilled in the art can fully understand how to implement the technical solution invented here.

[0066] Although some specific embodiments of the present invention have been described in detail by way of examples, it should be understood by those skilled in the art that the above examples are for illustration only and are not intended to limit the scope of the present invention. It should be understood by those skilled in the art that the above embodiments may be modified or some technical features may be replaced by equivalents without departing from the scope and spirit of the present invention. The scope of the present invention is defined by the appended claims.

Claims

1. A method for making a reduced model fermentation tank based on Kla, characterized in that: The following steps are involved: Step 1: Measure and obtain the Kla of large-scale fermentation tanks under different process parameters; Step 2: Use the database to mine the mechanical structure of the scaled-down model of the large-scale fermentation tank, and find the mechanical structure of the scaled-down model that is closest to the Kla of the large-scale fermentation tank under the same process parameters; Step 3: According to the obtained mechanical structure of the reduced model, a reduced model fermentation tank is manufactured; The mechanical structure includes: a turbine air collecting plate, a stirring aeration impeller, and a stirring shaft; The stirring shaft is arranged in the tank body of the reduced model fermentation tank; the stirring shaft is provided with a first fluid channel extending axially, and the stirring shaft is provided with a fluid inlet communicating with the first fluid channel; The turbine air collecting plate comprises a shell and a guide vane, the shell is sleeved on the outside of the stirring shaft, the diameter of the shell gradually decreases along a first direction, the first direction is parallel to the axial direction of the stirring shaft, one side of the guide vane is connected to the stirring shaft, and the other side is connected to the shell, the guide vane is spirally arranged along the first direction, the guide vane, the stirring shaft, and the shell are enclosed to form a guide channel, the guide channel is connected to the fluid inlet, and one end of the shell away from the bottom of the tank body is set to be an opening and is always located above the working liquid level in the tank body; The stirring aeration impeller is installed at one end of the stirring shaft close to the bottom of the fermentation tank, the stirring aeration impeller comprises a plurality of blades, a second fluid channel connected to the first fluid channel is opened on the blade, an outlet of the second fluid channel is arranged on the side of the blade opposite to the forward rotation direction of the stirring aeration impeller, and an opening direction of the outlet of the second fluid channel is a tangential direction of the stirring aeration impeller; The first direction is the direction from the top to the bottom of the fermentation tank; Step 4: Conduct actual Kla test on the manufactured scaled-down model fermenter and improve the scaled-down model until the test results are satisfactory.

2. The method for making a reduced model fermentation tank based on Kla according to claim 1, characterized in that: The Kla of the large-scale fermenter includes the maximum Kla of the large-scale fermenter.

3. The method for making a reduced model fermentation tank based on Kla according to claim 1, characterized in that: The process parameters include: specific input power P / V and ventilation volume vvm.

4. The method for making a reduced model fermentation tank based on Kla according to claim 1, characterized in that: The database is established through the correspondence between the mechanical structures accumulated in actual production and Kla.

5. The method for making a reduced model fermentation tank based on Kla according to claim 1, characterized in that: The actual Kla test is performed on the manufactured scaled-down model fermenter, and the scaled-down model is improved until the test result is satisfactory, including: performing an actual Kla test on the manufactured scaled-down model fermenter, and if the test result meets the Kla deviation requirement with the large-scale fermenter under the same process parameters, the test is terminated; if not, the cause is found and corrected until the deviation requirement is met.

6. The method for making a reduced model fermentation tank based on Kla according to claim 1, characterized in that: The mechanical structure also includes: the height-to-diameter ratio of the tank, the head space in the tank, the number of baffles, and the size of the baffles.

7. A fermentation tank prepared by any one of the methods of claims 1-6.

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