JPS61108370A - bioreactor - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed Description of the Invention] [Field of Application of the Invention] The present invention relates to a bioreactor, and particularly to a bioreactor, in which immobilized particles on which a reactant liquid and a biocatalyst are immobilized are made into a suspension state, and a gas is blown into this suspension. This invention relates to a bioreactor that causes a reaction.

[Background of the invention]

A suspension reaction tower is conventionally used in a bioreactor as a reactor that stores immobilized particles to which a biocatalyst is immobilized and causes a reaction with a liquid to be reacted.

This suspension reaction tower stores immobilized particles on which biocatalysts (enzymes, microorganisms, etc.) are immobilized in a suspended state, and brings the reaction solution into contact with the immobilized particles to produce the target product in a biological reaction such as an enzyme reaction. This is what we are trying to obtain.

This WI4 turbid reaction tower is less likely to be clogged with immobilized particles than a packed tower filled with immobilized particles.

Therefore, even if immobilized particles with a small particle size are used, the pressure loss is not large, and even if gel-like immobilized particles are used, the immobilized particles are not compressively deformed by liquid pressure, and gas is involved in one reaction. Stable operation is required for reactions that require a good mixing state in the metal body in the column, such as when the reaction is inhibited by substrates or products, or when processing raw materials containing impurities. is obtained.

However, the above-mentioned suspension reaction tower generally has the following problems.

That is, the first reason is that fluidity improves when the filling rate of immobilized particles contained in the suspension reaction tower is lowered, but conversely, when the filling rate is lowered, the amount of catalyst per tower volume becomes smaller. The amount of reaction decreases.

The second point is that the stabilized particles in the suspension reaction tower need to be suspended so that a uniform particle concentration distribution is achieved without some of them settling at the bottom, but the amount of ventilation becomes too large. In particular, immobilized objects formed of gel materials are destroyed by the mechanical impact of the flow caused by the aeration.

Therefore, as in the suspension reaction tower shown in Japanese Patent Publication No. 54-26972, the lower part of the reaction tower was made into a conical shape. Some types have a structure in which the compound particles gather near the center of the bottom of the column, so that a good fluidity state can be obtained without the liquid and fixed particles accumulating in some areas. However, in this suspension reaction tower, the cross section of the tower is not uniform in the height direction, so when comparing the towers with the same height, the volume per installation area is smaller than that of a reaction tower with a uniform tower diameter. Become. Therefore, high efficiency cannot be expected because the amount of immobilized substances stored inside is reduced.

Therefore, as described in JP-A No. 54-117379, a hollow draft tube is arranged in the suspension reaction tower to reduce the amount of ventilation compared to a suspension reaction tower without a draft tube. There is a turbidity reaction tower. Since this suspension reaction tower does not have a structure in which the cross section of the tower is not uniform in the height direction like the suspension reaction tower of Japanese Patent Publication No. 54-26972, the amount of immobilized material packed is lower than that of the conventional example. Although this increases compared to a turbid reaction tower, since a large amount of aeration must be generated when the suspension starts flowing, the immobilized material is likely to be destroyed, and especially when the filling rate becomes large, the amount of aeration increases proportionally. There is a risk that the immobilized material may be destroyed due to the increased size of the immobilized material.

[Purpose of the invention]

It is an object of the present invention to provide a biochemical solution that can control the amount of aeration necessary for fluidizing the suspension to such an extent that the immobilized substances are not destroyed even if the concentration of the immobilized substances packed into the suspension reaction tower is increased. The purpose is to provide a reactor.

[Summary of the invention]

The present invention detects the flow state of the immobilized particles and the reacted liquid in the suspension reaction tower, and according to the detection results, controls the suspension reaction tower so that the immobilized particles are not destroyed by the mechanical impact of the ventilation amount. This bioreactor is characterized by controlling the amount of ventilation.

That is, at the start of the reaction, the minimum amount of ventilation required to fluidize the suspension is supplied to the suspension reaction tower, and after fluidization has started, the minimum amount of ventilation necessary to maintain it is provided. This is particularly intended to prevent the immobilized material formed of gel material from being destroyed by mechanical impact.

[Embodiments of the invention]

Next, a preferred embodiment of the bioreactor according to the present invention will be described in detail with reference to the accompanying drawings.

FIG. 1 is an overall configuration diagram showing an embodiment of a bioreactor according to the present invention.

In the figure, the raw material storage 1 in which the reacted liquid is stored is a valve 21.
The pump 2 is connected to a piping 22 having a pump 2 . The pump 2 is connected to a pipe 23 in which a preliminary temperature regulator 3 is disposed, and this pipe 23 is connected to a raw material supply nozzle 12 in an immobilized enzyme suspension reactor 4 . A draft tube 7 is disposed within the immobilized enzyme suspension reactor 4, and a solid-liquid separation section 13 is further provided above the draft tube 7.

A ventilation nozzle 1 is installed in the lower part of the immobilized enzyme suspension reactor 4.
1 is provided, and this ventilation nozzle 11 has a
A ventilation pipe 24 having an m-valve 10 and venting from the blower 6
is connected. Refreshing.

A detection sensor 8 for detecting the flow state of the suspension is connected to the annular portion at the bottom of the draft tube 7 of the immobilized enzyme suspension reactor 4, and a signal S is transmitted from the flow state detection sensor 8. A signal S input from the regulator 9 is output to the control valve 10.

In the solid-liquid separation section 13 above the suspension reaction 114.

A pipe 14 for supplying a reaction liquid to the reaction liquid storage tank 5 is connected.

Next, the operation of this embodiment will be explained.

The substrate solution in the raw material storage tank 1 is extracted by a pump 2, heated to an optimum temperature by a preliminary temperature controller 3 provided midway, and then supplied to a reactor 4. The substrate fed into this reactor 4 is within the reactor 4 . The enzyme is converted into the target product by the immobilized particles, and the plumber 4
The reaction liquid is discharged through the reaction liquid tank 5.

The enzyme-immobilized particles in the reactor 4 include, for example, potassium alginate particles with an enzyme immobilized thereon.
The immobilized particles are suspended in the reactor 4. The suspension solution is a substrate-containing solution.

The enzyme reaction in the reactor 4 is carried out in a fluidized state by gas supplied from the blower 6 through the control valve 10 and through the piping 24. When this gas is supplied into the reactor 4, the flow of the suspension becomes the movement of the arrow shown in the figure. The dynamic pressure caused by the flow of the suspension is detected by the pressure detection sensor 8, and the flow rate of ventilation supplied to the reactor 4 is determined by the regulator 9 in accordance with the detected value of the detection signal S2, and the resulting output is The control valve 10 is actuated by the generated signal Ss, and the flow rate of ventilation passing through the pipe 24 is adjusted.

The minimum ventilation rate for maintaining the fluid state of the suspension in the reactor 4 varies depending on the filling rate of the immobilized particles, as shown in FIG. By keeping this aeration rate at a level that maintains fluidization, it is possible to prevent the immobilized particles from being destroyed by mechanical impact.

The regulator 9 controls the ventilation supplied into the reactor 4.

The control valve 10 is adjusted so that the air flow rate maintains fluidization.

Therefore, the specific routine of il[IIB by the regulator 9 will be explained as follows.

(1) Using the pressure sensor 8 installed at the lower part of the annular part of the reactor 4, the dynamic pressure PAII of the downward flow of the suspension is determined.

(2) Determine the descending flow velocity USA from the relational expression between the dynamic pressure P and the descending flow velocity UΩ, which have been calibrated in advance.

(3) Calculate ΔtJ2A=UjlA−Ujl○ by comparing the descending flow rate UaA with a value UAO set slightly above the lowest descending flow velocity that can maintain particle fluidization.

(4) If ΔUuA is positive and larger than the predetermined variable range ΔURO, a signal corresponding to the ΔUnA is calculated, and the calculation result is output as a signal to the valve 10 to reduce the amount of ventilation.

(5) If ΔUjlA obtained in (3) is positive and smaller than the variable area ΔU, the ventilation amount is maintained as it is.

(6) If ΔUAA obtained in (3) is negative, that Δ
A signal corresponding to the magnitude of UnA is calculated, and the calculated result is output to the valve 10 to increase the amount of air supplied into the reactor 4.

In the routine shown above, since the valve 10 is controlled by setting a constant lower side area ΔUflO, the valve can be adjusted less than when the valve is adjusted when ΔUnA is positive or negative.

In this example, in order to maintain a good fluidization state of the immobilized particles with a low flow rate of air, it is sufficient to set the aeration rate slightly higher than the fluidization maintenance aeration rate. In order to achieve fluidization, it is necessary to aerate at an aeration rate higher than the fluidization maintenance aeration rate, and then the aeration amount must be gradually lowered to a value slightly higher than the fluidization maintenance aeration rate. It is difficult to reduce the amount of ventilation without detecting the flow state of immobilized particles in the reactor. In addition, when the amount of air supplied to one reactor falls below the fluidization maintaining air flow rate and the circulating flow of the suspension stops, a diagonal line appears around the lower part of reactor 4, as shown in Figure 3. Immobilized particles are deposited as shown in 31. In this case, if an attempt is made to maintain the fluidization of the suspension by increasing the aeration rate, it is necessary to supply a large aeration rate that is greater than the aeration rate at which fluidization begins, and the immobilized particles are destroyed by mechanical impact. There is a possibility that

Next, FIG. 4 shows the relationship between the ventilation speed and the descending speed of the immobilized particles.

The 4th @ is when the density of the immobilized particles is 1.02.

The aeration rate for maintaining fluidization of immobilized particles is 0.03 (C!1
/8), and the aeration rate at the start of fluidization is 0.12 (am/8).
! When the flow rate is adjusted within this aeration rate, which is 1), the descending speed of the immobilized particles appears in the shaded area. Since the descending speed of the immobilized particles is greater than the free sedimentation speed, the sedimentation rate of the immobilized particles shown in FIG.
1 does not occur. Therefore, the deposition of immobilized particles tends to occur at the bottom of the annular part of the reactor. It is most preferable to provide the annular portion between the wall of 4 and the draft tube 7 at the bottom of the reactor.

Next, FIG. 5 shows the relationship between the cross-sectional area ratio of the draft tube, that is, the relative ratio of the cross-sectional area of one reactor 4 and the cross-sectional area of the draft tube, and the fluidization maintenance aeration rate.

As is clear in the figure, the cross-sectional area ratio is 0649 to 0.6
By using the draft tube described in Section 9, the air flow rate for maintaining fluidization can be lowered, thereby making it possible to prevent the immobilized particles from being destroyed by mechanical impact.

In this example, the dynamic pressure due to the flow of the suspension was detected as a means for detecting the fluid state of the immobilized particles.
In addition, the valve 10 can also be controlled by detecting the concentration of immobilized particles.

Next, another embodiment of the bioreactor according to the present invention will be described. Figure 6 shows the draft tube 7 in the reactor 4.
This is an embodiment in which a draft tube 61 with a reduced upper portion is used. Note that parts corresponding to those described in the embodiment shown in FIG.

In this example, the shape of the draft tube 7 is reduced in the upper part, as compared to the conventional straight draft tube in which the cross-sectional area ratio between the draft tube and the reactor is 0.5 to 0.7. As shown in Figure 2, when the draft tube is aerated at a low airflow rate close to the fluidization maintenance airflow rate, the rising air bubbles tend to cause uneven flow, which causes the suspension to flow out from the top of the draft tube unevenly. 1 A uniform circulation flow is not formed in the annular portion between the wall of the reactor 4 and the draft tube.

On the other hand, if a draft tube is used as in this embodiment, there is no problem of uneven flow of the suspension flowing inside the draft tube, as shown in FIG.

As the draft tube used in the main flow example, in addition to the draft tube shown in FIG. 8, it is also possible to use a conical draft tube whose upper part is reduced as shown in FIGS. 7 and 8.

In addition, as shown in Fig. 2, when a draft tube with a reduced upper part is used as in this example, the fluidization maintaining air velocity relative to the filling rate of immobilized particles is reduced compared to a conventional straight draft tube. can do. That is, as shown in FIG. 11, the fluidization maintenance ventilation rate with respect to the filling rate of immobilized particles is as follows: when using a draft tube with a reduced upper part (A), the conventional cross-sectional area ratio is 0.5~
It has been found that in the case of a straight draft tube of 0.7, the amount can be reduced compared to CB).

Furthermore, as shown in Figure 12, the liquid mixing time of a suspension reactor equipped with a draft tube with a reduced upper part (A in the diagram)
is shorter than the liquid mixing time (B in the diagram) of a suspension reactor equipped with a conventional straight draft tube.
It was found that the mixing effect of the raw material solution containing the substrate and the immobilized particles was large in the reactor using the draft tube with the upper part reduced. Therefore, the amount of ventilation per reactor can be further reduced.

Next, six specific embodiments of the bioreactor according to the present invention will be described.

Experimental Example 1 The bioreactor shown in Figure 6 was used to contain a suspension of immobilized particles, and the suspension was fluidized by venting air from the bottom 11 of the thermal reactor measured with a flowmeter. The reactor 4 had a diameter of 300 mm.

The material is acrylic and allows the flow state of particles inside the tower to be observed from the outside. Note that if the tilting state can be observed, the ventilation amount can be adjusted manually, but if one reaction takes a long time.

It is necessary to automatically control the ventilation amount using a detection sensor and a regulator.1 The draft tube 7 installed inside the reactor 4 has a diameter of 210 m at the lower part, a diameter of 100 m at the upper part, and a conical part in the middle. They are connected by draft tubes and have a total height of 600m.

The immobilized particles contained in the reactor are particles of calcium alginate prepared by a conventional method, and the solution in which the immobilized particles are suspended is tap water containing calcium chloride. The immobilized particles were filled into the reactor so that the apparent particle volume was 60% of the suspension raw material 50j1 inserted into the reactor.Next, the pressure sensor 8, the regulator 9. Valve 1
0. When the blower 6 was operated, the valve 10 described above was operated and fluidization of the suspension was started at an air flow rate of 0.12a"s. After the fluidization was started, the regulator 9 The valve 10 was operated, and the aeration rate was gradually reduced to 0.03 CIl/S. It was confirmed that a good fluidity state could be maintained without depositing immobilized substances in the bottom annular portion of the reactor.

〔Effect of the invention〕

As explained above, according to the present invention, since the reaction can be carried out while detecting the fluidization state of the suspension in the suspension reactor, the fluidization start speed and maintenance speed can be kept to a minimum. Therefore, the reaction can be carried out efficiently while preventing mechanical destruction of the immobilized material on which the biocatalyst is immobilized.

[Brief explanation of the drawing]

1 and 6 are general configuration diagrams showing one embodiment of a bioreactor according to the present invention, and FIGS. 2 and 11 are graphs showing the relationship between the filling rate of immobilized particles and the fluidization maintenance aeration rate, Fig. 3 is a diagram showing the flow state of a suspension in a conventional draft tube, Fig. 4 is a graph showing the relationship between the aeration rate and the descending speed of immobilized particles, and Fig. 5 is a graph showing the cross-sectional area ratio of the draft tube. Graph showing the relationship between fluidization maintenance aeration rate. Figures 7 and 8 are diagrams showing the flow state in the draft tube, Figures 9 and 10 are diagrams showing other draft tubes used in the bioreactor shown in Figure 6, and Figure 12. is a graph showing the relationship between ventilation speed and liquid mixing time. 4... Reactor, 5... Reaction liquid mixing tank, 6... Ventilation blower. 7...Draft tube, 8...Pressure sensor, 9
... Regulator, 10... Ventilation valve, 11... Ventilation nozzle.

Claims (1)

[Claims] 1. A reactor in which a suspended solution of immobilized particles on which a predetermined biocatalyst is immobilized is stored, a hollow draft tube provided in the reactor, and a hollow draft tube provided in the reactor; a raw material supply means for supplying a substrate-containing raw material containing a substrate that reacts with the immobilized particles; and supplying a gas for inducing a liquid flow to a suspension solution to which the substrate-containing raw material is supplied in the reactor. In the bioreactor, the bioreactor is equipped with a gas supply means for reacting the substrate-containing raw material with the immobilized particles, and a reactant extraction means for taking out the reactant produced by the reaction of the substrate-containing raw material with the immobilized particles. a detection means for detecting and outputting a predetermined detection signal; and when the output amount of the detection signal is above a predetermined value, the flow rate of the gas of the gas supply means is reduced; A bioreactor comprising: a gas flow rate control means for increasing the gas flow rate of the gas supply means to maintain a predetermined flow state of the immobilized particles. 2. Claim 1, characterized in that the upper end of the draft tube has a structure in which the opening area is narrower than that of the lower end.
Bioreactor as described in Section.