JP2573952Y2 - Reactor - Google Patents

Description

[Detailed description of the invention]

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a reactor, and more particularly, to a reactor for efficiently performing a reaction using an immobilized carrier, for example, a bioreactor.

[0002]

2. Description of the Related Art In the biotechnology-related field, which has recently become popular, an immobilized carrier is put in a reaction vessel, microorganisms and enzymes are immobilized in the immobilized carrier, and a substrate solution (reaction solution) is pumped out by a pump or the like. It has been practiced to react with immobilized microorganisms or enzymes to obtain useful substances.

[0003] A reactor for performing such a reaction generally uses a tube made of glass or the like, a so-called column tube as a reaction tank, and immobilizes the microorganisms, enzymes and the like on the column tube. The carrier is put into the reactor, the column tube is kept at the optimum temperature by a warm water jacket, etc., the substrate solution is pumped from above or below by a pump or the like, and the reaction is carried out. Have been.

[0004]

However, in a reactor having such a structure, the immobilized carrier often becomes tightly packed in the reaction tank. In such a case, the substrate solution passes through a place and a path which are easy to pass through. In some cases, a phenomenon called channeling, in which a passage of the substrate liquid is formed in the immobilized carrier layer, may occur.

[0005] When such channeling occurs, the substrate solution reacts only with microorganisms and enzymes near the passage,
Since it passes without reacting with the majority of other immobilized microorganisms and the like, the reaction efficiency is significantly reduced.

[0006] Further, a part of the immobilized carrier layer is firmly solidified, and a state in which the substrate solution cannot pass through, that is, a phenomenon called so-called consolidation may occur. In this case, the reaction efficiency also becomes extremely low.

[0007] Because of the phenomenon of channeling and consolidation, the reaction efficiency of column type reactors has not been increased conventionally, and various methods have been devised in this field to overcome this. .

[0008] That is, a shelf-like thing in which the immobilized substance is placed in the column is attached in multiple stages, and a method in which the substrate solution is flowed during this time, or the column is turned sideways and rotated, and the immobilized carrier is rotated by rotating the column. To prevent channeling and consolidation.

[0009] However, these methods are complicated due to the use of this method, and must be very expensive due to considerations required for slidability of rotating parts and prevention of liquid leakage. At present, downsizing involves considerable difficulty.

Accordingly, the present invention provides a reactor which can increase the efficiency of the reaction between a substrate and an immobilized carrier without causing channeling and consolidation which are disadvantages of a conventional reactor, and which can be manufactured at low cost. The purpose is to provide.

[0011]

SUMMARY OF THE INVENTION The reactor of the present invention has been made in view of the above points, and has a structure in which a plurality of spherical bodies are filled in a bottom portion of a reaction tank and a reaction solution is supplied to the reaction tank. The distal end of the liquid tube is opened in the packed layer of the spherical body.

[0012]

According to the above configuration, the substrate liquid supplied by the liquid sending pipe flows out of the tip of the liquid sending pipe into the packed bed of spheres at the bottom of the reaction tank, and when passing between the spheres, The energy of the flow rises from the spherical body layer while being dispersed and changed into a flow having a generality. At this time, by appropriately setting the flow rate of the substrate solution according to the specific gravity of the substrate solution and the specific gravity of the immobilized carrier, the immobilized carrier can be brought into a uniform flow state, and the carrier and the substrate solution can be efficiently used. You can make good contact.

[0013]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in more detail with reference to the embodiments shown in the drawings.

FIG. 1 shows an embodiment of the reactor of the present invention. This reactor comprises a reactor body (reaction tank) 1, a flow pump 2 for giving a flow to the substrate liquid in the reaction tank 1, and a supply pump for supplying a fresh substrate liquid into the reaction tank 1. A substrate tank 3 and a substrate pump 4; and a product tank 5 for receiving a product generated in the reaction tank 1.
And a pipeline connecting them.

The reaction vessel 1 has a jacket 11 on the outer circumference, an upper portion having an enlarged diameter, and a bottom member 13 having a spherical bottom attached to a lower portion of the body portion 12.
And a lid member 14 attached to the upper part of the main body 12. An overflow port 51 communicating with the product tank 5 is provided on the upper side wall of the main body 12, and the bottom member 13 has , Many spherical bodies 6 are filled. The bottom member 13 and the lid member 14 are respectively connected to the clamp 1
5 is attached to the main body 12.

The reaction tank 1 can be made of glass, stainless steel, plastics, or the like, but is sometimes made of glass because it may require a sterilization operation and can check the internal flow state. It is desirable.

The flow pump 2 is attached to the lid member 14.
A liquid feed pipe 21 and a withdrawal pipe 22 communicating with the substrate pump; a substrate feed pipe 23 communicating with the substrate pump 4;
, A chemical liquid inlet 25 and a thermometer 26 are provided. In addition, as the sensor 24, for example, the pH of the substrate solution is used.
Sensor for measuring pH, DO for measuring dissolved oxygen concentration
A sensor, a temperature sensor for measuring temperature, or the like is used according to the purpose.

The spherical body 6 is made of a material having a considerable difference in specific gravity from the substrate liquid, and is chemically and physically stable. It must be a substance that does not move, and when using microorganisms, it must be able to withstand sterilization operations such as autoclaves.

For this reason, the spherical body 6 may be a glass sphere, a stainless sphere, a Teflon-coated stainless sphere, a gold sphere, or the like, but the glass sphere or the stainless sphere is optimal in consideration of the price and the like. The shape of the spherical body 6 is desirably spherical, but it is not necessarily required to be spherical, and it is not necessary that all of them have the same shape and size. The size of the spherical body 6 depends on the scale of the reactor and the flow rate of the reaction solution (substrate solution).
A diameter of about 5 mm is suitable.

The liquid feed pipe 21 for flow is provided so that the tip thereof reaches the bottom of the bottom member 13 through the center of the reaction tank 1 so that the substrate liquid is filled in the bottom member 13. It is set so as to flow out to the lower part of the layer of the formed spherical body 6.

The drawing tube 22 is provided so that its tip is located below the substrate level surface in the reaction tank 1, that is, is located slightly below the overflow port 51.

Here, the carrier for immobilization used in the reactor having the above-mentioned structure must not float in the substrate solution and must sediment. This is based on the premise that there is some difference in the specific gravity between the substrate and the carrier,
It must be able to withstand sterilization operations such as autoclaves. For this reason, as a carrier for immobilization, a porous glass bead having a diameter of 0.4 to 1 mm is optimal, but other materials can be used as long as the above conditions are satisfied.

In using the reactor constructed as described above, first, a carrier for immobilizing microorganisms, enzymes, and the like is put on the spherical body 6 filled in the bottom of the reaction tank 1.
If necessary, a sensor or the like is installed, and when immobilizing microorganisms, sterilization is performed using an autoclave or the like.

Next, microorganisms, enzymes, and the like are immobilized on the immobilization carrier in the reaction tank 1 by a well-known method individually specified for the immobilization target. Note that a carrier on which microorganisms, enzymes, and the like are immobilized may be added later. Next, if necessary, a fresh substrate liquid is fed from the substrate tank 3 by the substrate pump 4 through the substrate feed pipe 23 so that the substrate level surface comes to the lower end of the overflow port 51.

At the same time, constant temperature water adjusted to the optimum temperature is circulated through the jacket 11 using an appropriate constant temperature water circulating device, and the inside of the reaction tank 1 is set to the optimum temperature.

Then, the flow pump 2 is operated to suck up the substrate from the drawing tube 22 and to flow out into the spherical body 6 from the tip of the flow liquid transfer tube 21. The flowing out substrate liquid passes through the space between the filled spherical bodies 6, and its flow is dispersed, and the flow is adjusted not to a directional flow but to a generalized flow, and generally along the spherical surface of the hemispherical bottom surface. Rise and
This is a flow that pushes the immobilized carrier upward.

Thereafter, the carrier rises substantially along the inner wall of the reaction vessel 1 and is pushed upward to a certain ascending limit H from the relationship between the flow rate and the specific gravity difference between the substrate solution and the carrier. . At this time, the flow rate of the substrate solution can be rapidly reduced in this portion by forming the upper structure of the reaction tank 1 as the above-mentioned diverging structure that widens upward as described above. Can be suppressed.
Note that, in this case, it is most preferable to have a divergent structure at an angle of 60 degrees with the horizontal plane.

Part of the substrate liquid that has risen to the upper part of the reaction tank 1 is sucked up from the drawing pipe 22, and the other part is fed to the liquid sending pipe 2.
It descends along 1. Accordingly, the immobilized carrier is pushed up to a certain ascending limit as shown by the arrow R in the figure by the ascending flow along the inner wall of the reaction vessel 1, and then descends to the lower part of the vessel by this descending flow, and again. It becomes a flowing state that rises due to the upward flow.

By this flow, the substrate and the immobilized carrier are integrated and flow as a solid-liquid fluid, so that the above-described compaction and channeling do not occur at all, and the substrate and the immobilized microorganisms, enzymes, etc. The reaction between them proceeds uniformly and efficiently, and high reaction efficiency is obtained. In addition, since the fixed carrier maintains a certain ascent limit as described above, it is not sucked at all through the drawing tube 22.

Further, at the stage when the reaction has progressed, fresh substrate liquid is supplied from the substrate tank 3 to the substrate inlet pipe 2 by the substrate pump 4.
An appropriate amount is fed into the reaction tank 1 via 3 to allow the reaction to proceed continuously. At this time, if the positional relationship between the substrate inlet pipe 23 and the overflow port 51 is appropriately set, the flow of the substrate liquid in the reaction tank 1 causes the fresh substrate to mix immediately, so that the fresh substrate is directly There is almost no outflow from 51 to the product tank 5.

Then, by the introduction of the fresh substrate, the reaction product overflows from the overflow port 51 to the product tank 5 through the connecting pipe.

During this time, the state of the substrate solution can be monitored by the sensor 24, and a chemical solution for maintaining or changing the state of the substrate solution can be supplied from the chemical solution inlet 25. For example, the pH of the substrate solution is measured using a pH sensor as the sensor 24, and based on the result, the pH of the substrate solution can be maintained at a desired value by introducing an acid or an alkali solution. It is also possible to measure the dissolved oxygen concentration of the substrate solution using a DO sensor instead of a pH sensor, or to control the temperature of the substrate solution by controlling a constant temperature circulating device using a temperature sensor.

Here, the results of experiments performed to confirm the effects of the present embodiment will be described.

On a hemispherical bottom of a reaction vessel 1 having a total volume of 2 liters, 200 m glass spheres having a diameter of about 5 mm
, and 700 ml of a porous glass-immobilized carrier having a diameter of 0.4 to 1 mm.
The PY medium (specific gravity 1.02) was put into the lower end of the overflow port 51. Next, each pipe was connected, the flow pump 2 was operated to circulate the substrate liquid, and the carrier was caused to flow.

Thereafter, the flow rate was adjusted, the flowing volume at that time was measured, and the state was observed. As a result, the volume flowing at a flow rate of 1.3 liter / min is 780 ml,
870 ml at 1.5 liter / min, 900 ml at 2.3 liter / min, 960 ml at 3.1 liter / min
It became. As a result of observing the state of the flow, the state at the time when the flow rate was 2.3 liters / minute was the best.

Next, when a similar experiment was performed without inserting a glass bulb, when the flow rate was 1.5 liters / min or less, the bottom portion hardly flowed, and slightly flowed at 1.8 liters / minute. The flow volume was 790 ml and the flow volume was 900 ml at 2.4 l / min.
The flow near the bottom was too vigorous, and the carrier did not seem to be able to retain its normal form.

As described above, glass spheres were charged, and the flow rate was 2.3.
After continuing the flow for 7 days at a rate of 1 liter / min, the carrier was observed with a microscope. As a result, almost no destructive wear of the carrier was observed. On the other hand, when the same experiment was conducted without glass balls, observation under a microscope revealed that many carriers were broken and worn.

In the case where no glass bulb is inserted, if the opening of the tip of the flow liquid transfer pipe 21 is slightly deviated from the center of the reaction tank 1, a non-uniform flow is generated due to the uneven flow, whereas When a glass ball was inserted, a uniform flow state was obtained even if the axis was slightly shifted.

FIGS. 2 to 4 show another embodiment of the present invention. The same elements as those shown in FIG. 1 are denoted by the same reference numerals, and detailed description thereof will be omitted.

FIG. 2 shows a structure in which the reaction tank 1 has an integral structure including a bottom portion, and a lid member has a structure in which a silicon stopper 16 or the like is fitted to the upper part of the reaction tank 1. This allows
The reaction tank 1 can be simplified and reduced in size, and can be provided at a lower cost than that shown in FIG. It is desirable that the reaction tank 1 be made of glass so that the contents can be observed, as in the case described above.

Further, the reactor shown in this example is for improving the reaction efficiency with the substrate by flowing the immobilized carrier in the same manner as described above, but the substrate solution is supplied from the substrate tank 3 by the substrate pump 4. After being supplied into the reaction tank 1 through the substrate feed pipe 23 to form a flow for raising the immobilized carrier, the flow is circulated through the path from the overflow port 51 to the substrate tank 3.

Therefore, the reactor has a configuration of a batch type. However, this reactor functions as a continuous reactor, and the substrate in the substrate tank 3 in addition to the substrate in the reaction tank 1 can contribute to the reaction. Therefore, a large amount of reaction products can be obtained.

FIG. 3 shows that two reaction tanks are used, the reaction tank 1 and the reaction tank 1 'are connected, and the overflow port 51 of the reaction tank 1 and the substrate inlet pipe 23' of the reaction tank 1 'are connected to each other. Are connected by a conduit 52. Each component on the side of the reaction tank 1 ′ is indicated by adding a dash to the reference numeral of each component corresponding to the reaction tank 1.

That is, in the apparatus of this embodiment, different microorganisms or enzymes are immobilized in the reactor 1 and the reactor 1 ', respectively, and the jackets 11 and 11 are respectively supplied from the constant temperature water circulation devices 61 and 61'. By circulating constant-temperature water at a predetermined temperature through the ′, different reactions can be continuously performed, and a completely new product can be produced quickly and efficiently.

In this case, two or more units can be connected and reacted continuously if conditions are satisfied, instead of two units.

FIG. 4 shows the reaction vessel 1 for further simplification.
From which the jacket is removed, and is immersed in a constant temperature water tank 62 as shown in the figure. For this reason, the reaction tank 1 can be further reduced in size and cost, and is most suitable as school teaching materials for junior high schools, high schools and the like.

As shown in FIGS. 2 to 4, as described above, the spherical liquid 6 filled in the bottom of the reaction tank 1 is supplied from the liquid feed pipe 21 for flow or the substrate feed pipe 23 to the substrate liquid. By causing the immobilized carrier to flow out, the above-mentioned flow can be caused in the immobilized carrier, consolidation and channeling can be prevented, and the substrate solution and the immobilized carrier can be sufficiently contacted to increase the reaction efficiency. it can.

Furthermore, a uniform flow state can be obtained even if the flow liquid supply pipe 21 for flowing out the reaction liquid into the spherical body 6 or the substrate supply pipe 23 does not coincide with the central axis, so that setting of the apparatus is easy. Therefore, failures due to setting mistakes can be greatly reduced, so that the overall efficiency can be greatly improved together with the improvement of the reaction efficiency.

FIG. 5 shows that the bottom member 13 at the bottom of the reaction tank 1 shown in FIG. 1 is replaced with a bottom member 16 for a packed bed, and a perforated plate 17 is provided between the bottom member 16 and the reaction tank 1 main body 12. The reaction vessel 1 is sandwiched and filled with the immobilizing carrier 18 for filling.
In this case, the liquid supply pipe 21 is pulled up to just above the eye plate.

It is desirable to select an immobilization carrier 18 to be filled with a pressure loss as low as possible. For example, it is preferable to use a carrier having an extremely small pressure loss such as a cylindrical porous glass carrier shown in the figure. However, the pressure is not limited to this, and any pressure loss can be used.

In this embodiment, fresh substrate is sent from the substrate tank 3 by the substrate pump 4 to the bottom of the reaction tank 1 from the liquid feed pipe 21 and reacts with the immobilized microorganisms or enzymes upward from the bottom. Proceed to overflow port 5
1 to the product tank 5. During this time, a gas such as air, nitrogen, or carbon dioxide can be supplied as needed from a gas supply port 19 attached below the bottom member 16 for the packed bed.

Thus, the reaction tank 1 shown in FIG.
By simply changing the bottom member, it can be used as the above-mentioned fluidized bed type or as a packed bed type. By making the bottom member detachable and replaceable in this way, a reaction type according to the purpose can be achieved. The reactor can be selected, and the reactor can be used efficiently.

[0053]

[Effects of the Invention] As described above, according to the present invention,
The carrier on which microorganisms, enzymes, and the like are immobilized can be made to flow uniformly, and the reaction can proceed uniformly and efficiently without causing phenomena, such as channeling and consolidation, which have been problematic in the past.

Further, by making the bottom member detachable and replaceable, it can be used as a conventional packed bed type reactor simply by changing the bottom of the reaction tank. Because it can be used for both layer type, it can be used very economically and conveniently.

Further, since the structure is relatively simple, the production can be simplified, and a large number of simplified ones can be purchased, so that many kinds of experiments can be performed simultaneously in parallel, and the experiment period is greatly extended. It is possible to shorten it. That is, by miniaturizing the reaction vessel in this way, a plurality of experiments can be performed simultaneously and in parallel using different microorganisms or enzymes under different conditions. It has an excellent effect of preventing consumption.

Since the simplified one is easy to handle, it can be widely used for school education.

Although the present invention mainly targets microorganisms and enzymes to be immobilized, it can be used as an affinity chromatograph by selecting the properties of the substrate solution and the immobilized carrier.

[Brief description of the drawings]

FIG. 1 is a system diagram showing an embodiment of the reactor of the present invention.

FIG. 2 is a system diagram showing an embodiment of a simplified reactor.

FIG. 3 is a system diagram showing an example in which two reactors are connected in series.

FIG. 4 is a system diagram showing an embodiment of a reactor obtained by further simplifying the reactor shown in FIG. 2;

FIG. 5 is a system diagram showing an example when the reactor shown in FIG. 1 is a packed bed type.

[Explanation of symbols]

1. Reaction tank 2. Flow pump 3. Substrate tank
DESCRIPTION OF SYMBOLS 4 ... Substrate pump 5 ... Product tank 6 ... Spherical body 11 ... Jacket 12 ... Body part 13 ... Bottom member 14 ... Lid member 15 ... Clamp
Reference numeral 21: liquid supply pipe for flow 22: extraction pipe 23: substrate supply pipe 51: overflow port

Claims (3)

(57) [Scope of request for utility model registration] 1. The method according to claim 1, wherein a plurality of spheres are filled in the bottom of the reaction tank, and a tip of a liquid feed pipe for supplying a reaction solution to the reaction tank is opened in the packed layer of the spheres. Reactor. 2. The reactor according to claim 1, wherein the reaction tank has a bottom portion for filling the spherical body detachably formed with the reaction tank body. 3. The reaction according to claim 1, wherein the reaction tank has a drawing pipe or an overflow port for drawing out a reaction solution at an upper part, and a diameter near the drawing pipe or the overflow port is enlarged. vessel.