JPH088856B2 - Airlift reactor for fed-batch culture - 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 an airlift reactor for fed-batch culture.

[0002]

2. Description of the Related Art Fed Batch Culture is a method for increasing the amount of medium with the growth of cells when the cells are cultured at a high concentration to obtain its metabolites.
re) is known. A jar fermenter equipped with a stirring device, an aeration device, and a cooling device is generally used for this culture.

By the way, recently, a large amount of substances are produced by using cells that have undergone cell fusion or DNA recombination. However, if the conventional culture means is directly scaled up, various problems occur.

That is, in the conventional fed-batch culture, in many cases, the reactor 1 as schematically shown in FIGS. 3 and 4 is used. The reactor 1 shown in FIG. 3 is used for a small scale, and the reactor shown in FIG. 4 is used for a large scale. An agitator 2 is provided inside the reactor 1. In the case of FIG. A stirring shaft 3 is vertically installed in the tank, and a plurality of stirring blades 4, 4 ...
It is structured to rotate and stir by. In FIG. 3, 6 is a cooling jacket, and 7 is an air supply system.

In the case of FIG. 4, an air supply system 7 is vertically provided above the stirrer 2, a draft tube 8 is provided around the air supply system 7, and a cooling coil 9 is provided around the draft tube 8.

[0006]

However, the conventional agitator has not only a complicated structure but also
Since the blades 4 rotate, the shearing force against the bacterial cells becomes large, and the flow of the liquid in the tank is often disturbed, which causes frequent back mixing, resulting in performance deterioration.

Further, in the case of a large-capacity reactor of 5 m ³ or more, a cooling coil 9 is often required inside as shown in FIG. 4, and therefore an internal coil 9 support mechanism is required. The presence of the compound deteriorates detergency and makes microbial control extremely difficult.

Further, when the agitator 2 is used for the purpose of preventing sedimentation of bacterial cells and shearing bubbles, the capacity of the electric motor increases drastically with scale-up, making it difficult to seal a shaft such as a mechanical seal. There is a problem that is required.

In view of the above, the present invention has a structure that does not use a stirrer, has a small backflow, and is capable of both batch feeding and continuous feeding, has a low shearing force against bacterial cells, and has a high reaction efficiency. It is an object of the present invention to provide an air-lift type reactor for fed-batch culture that can be used even at a position.

[0010]

[Means for Solving the Problems] As a means for solving the problems of the above-mentioned prior art, the present invention comprises a culture tank main body and an inner cylinder installed in the tank main body. The cylinder is supported in the tank main body so that the lower part thereof communicates with the lower part of the tank main body, and a plurality of weir windows are provided in a row in the circumferential direction on the peripheral surface of the inner cylinder at a predetermined height position. The upper peripheral edge serves as an upper weir, and an air supply system and a medium supply system are connected to the lower part of the tank main body, and liquid that overflows from the weir window or the upper end weir of the inner cylinder and enters between the tank main body and the inner cylinder. The cooling means for cooling the internal cylinder is provided, and the liquid cooled and descending rises in the inner cylinder to generate a natural circulation flow by utilizing the difference in specific gravity between the liquid inside and outside the inner cylinder. And

[0011]

The culture solution is supplied into the tank body through the medium supply system and rises in the inner cylinder together with the air supplied into the tank body through the air supply system. Depending on the water level of the culture solution, it overflows from the weir window in either the vertical direction of the inner cylinder to the outside of the inner cylinder, enters between the tank body and the inner cylinder, is cooled by the cooling means of the tank body, and becomes a downward flow, Then, the natural convection occurs by repeating the process of entering the inner cylinder again and rising. In this case, when there is a large amount of liquid in the tank body, it overflows from the upper end weir of the inner cylinder, and overflows from one of the weir windows below it depending on the water level of the liquid and circulates. Stirring is performed regardless of the liquid amount regardless of continuous feeding. By incorporating a cooling pipe group around the tank body, the temperature of the culture solution can be controlled by controlling the supply amount of the refrigerant or the temperature thereof.

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below with reference to the embodiments shown in the drawings. FIG. 1 is a front view showing a cross section of a tank body 10 of an embodiment of an airlift reactor for fed-batch culture according to the present invention. The tank body 10 has a rigid cylindrical shape. The inner cylinder 11 is erected concentrically, and the lower portion of the inner cylinder 11 and the lower portion of the tank body 10 are supported by the support portion 12 in a communicating state.

The inner cylinder 11 has a height such that a space 13 is left above the inside of the tank main body 10, and an upper end dam 14 which is cut out in a sawtooth shape is formed on the upper peripheral edge of the inner cylinder 11, and the upper and lower intermediate portions are formed in the vertical direction. At the position, a plurality of weir windows 15 and 16 are provided at the same level in the circumferential direction for a required number of steps (two steps in the figure). The weir window 15 is the same as the upper end weir 14,
It has an inverted triangular hole structure in order to improve the stirring property when overflowing.

A pipe 17 from a pressure air source is connected to a lower portion of the tank body 10 through a filter 18 and a valve 19 on the way, and a pipe 20 from a culture solution supply source is provided at a lower center of the tank body 10. It is connected via a pump 21 and a valve 22. Further, a product take-out pipe 23 is connected to the lower bottom portion of the tank body 10 via a valve 24, and an exhaust pipe 25 is connected to the upper portion of the tank body 10 via a valve 26.

A cooling jacket 27 is attached to an outer peripheral portion of the tank main body 10 within a height range of the inner cylinder 11, a refrigerant (cooling water) inlet 28 is provided at a lower portion thereof, and a refrigerant discharge portion is provided at an upper portion thereof. An outlet 29 is provided, a refrigerant supply pipe 30 is connected to the refrigerant inlet 28, and a refrigerant discharge pipe 31 is connected to the outlet 29. Reference numeral 32 denotes a refrigerant temperature control device.

A group of cooling pipes 33, 33 ... Is arranged between the tank body 10 and the inner cylinder 11 below the cooling jacket 27. The cooling pipe 33 includes an upper plate 34 liquid-tightly fixed between the tank body 10 and the inner cylinder 11 at a position near the lower end of the cooling jacket 27, and the tank body 1 as well.
The upper and lower ends are inserted into and supported by the lower plate 35 fixed near the lower part of 0, and the upper surface of the upper plate 34 and the lower surface of the lower plate 35 are connected by the cooling pipes 33, 33 ... A space portion between the upper plate 34 and the lower plate 35 serves as a cooling jacket 36, and a branch pipe 30a of the refrigerant supply pipe 30 is provided therein.
And the branch pipe 31a of the refrigerant discharge pipe 31 is connected.

Therefore, when the culture solution is supplied by the pump 21 through the pipe 20 of the culture solution supply system in the lower part of the tank body 10 and the air (sterile air) is supplied through the pipe 17 of the air supply system, the air becomes bubbles in the culture solution. As a result, an ascending flow occurs along the inside of the inner cylinder 11 in the tank body 10. At this time, depending on the water level of the culture solution, it overflows from the weir window 16 or 15 of the inner cylinder 11 to the outside of the inner cylinder 11 and enters between the inner cylinder 11 and the tank body 10.

Since the inner circumference of the tank body 10 is cooled by the refrigerant supplied to the cooling jacket 27, a downward flow is generated along the inner circumference surface of the tank body 10, and the inside of the cooling pipes 33, 33 ... While descending through, it is cooled by the cooling jacket 36 and reaches the lower part of the tank body 10,
Then, an upward flow is again generated from the lower part of the inner cylinder 11
As a result, natural convection as indicated by an arrow is generated so as to circulate in the inside, and the circulation occurs, and stirring occurs.

When the culture liquid in the tank body 10 has a high water level, it overflows from the upper end weir 14 of the inner cylinder 11 and circulates in the same manner. Therefore, regardless of the water level in the tank body 10,
In particular, a circulating flow can be generated even at the lowest water level.

[0020]

As described above, according to the present invention, since it is possible to cause natural circulation in the reactor without using a stirrer, the shearing force against the bacterial cells is small,
Does not damage the cells. In addition, the inner cylinder is used as an ascending flow path, and by overflowing the weir window formed on the peripheral surface of the inner cylinder to circulate the structure, a structure with less backflow can be formed and the liquid level can be increased regardless of the liquid level. Even if the weir window is immersed, it can be circulated through the weir window due to the liquid level difference between the inside and outside of the inner cylinder, and a reactor with high reaction efficiency can be obtained.

[Brief description of drawings]

FIG. 1 is a vertical sectional front view showing an embodiment of a reactor according to the present invention.

FIG. 2 is a perspective view in which a portion showing details of a cooling pipe portion in FIG. 1 is a section.

FIG. 3 is a schematic sectional view showing a conventional reactor.

FIG. 4 is a schematic vertical sectional view showing a conventional large-sized reactor.

[Explanation of symbols]

 10 Tank Main Body 11 Inner Cylinder 14 Upper End Weir 15, 16 Weir Window 21 Pump 23 Extraction Pipe 25 Exhaust Pipe 27 Cooling Jacket 33 Cooling Pipe 36 Cooling Jacket

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Shigeru Takehara Masaru Jingumae 6-26-1, Shibuya-ku, Tokyo Kirin Brewery Co., Ltd. (56) Reference JP-A-63-251077 (JP, A)

Claims (1)

[Claims] 1. A culture tank main body and an inner cylinder installed in the tank main body, wherein the inner cylinder is supported in the tank main body so that a lower part thereof communicates with a lower part of the tank main body. A plurality of weir windows are circumferentially arranged in a row at a predetermined height on the peripheral surface, and the upper peripheral edge serves as an upper weir, and an air supply system and a medium supply system are connected to the lower part of the tank body. A cooling means for cooling the liquid that has overflowed from the weir window or the upper end weir of the inner cylinder and has entered between the tank body and the inner cylinder, and the cooled and lowered liquid rises in the inner cylinder. As a result, an airlift reactor for fed-batch culture is characterized in that a natural circulation flow is generated by utilizing the difference in specific gravity between the liquid inside and outside the inner cylinder.