JPH078264A - Bioreactor - Google Patents

Abstract

PURPOSE:To provide a bioreactor capable of significantly lengthening the residence time of bubbles in a culture fluid, thus markedly improving gas feed efficiency compared with conventional cases. CONSTITUTION:A culture tank 1 is made in a vessel form of flat plate type, and the inside of the tank is provided with a partition plate 4 extended from the proximity of the bottom of the tank to the proximity of the upper level of a culture fluid 3 so as to partition the inside space of the tank 1 at the center in its thickness direction, and agitating blades 5 and a sparger 6 are installed under the partition plate 4 and off to the above the agitating blades 5, respectively. The agitating blades 5 are revolved in the arrow direction by a motor 7. The sparger 6 is so designed that several fine holes 6b are bored through a pipe 6a, and a gas piping 8 is connected to one end of this sparger 6.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bioreactor used for culturing various living organisms, and more particularly to a bioreactor for culturing while supplying gas into a culture solution.

[0002]

2. Description of the Related Art Generally, in a liquid-type bioreactor, in addition to supplying a nutrient source necessary for cell growth and production of useful substances using cells by dissolving it in a culture solution, oxygen is supplied. Nutrient sources such as carbon dioxide and carbon dioxide are supplied by bubbling gas into the liquid.

As such a bioreactor, for example, a bioreactor in which a sparger for generating bubbles is arranged on the bottom of a cylindrical culture tank and stirring blades are arranged on the sparger is known. Most used. The role of the stirring blades provided on the sparger is to stir the culture medium and prevent the cells from settling at the bottom of the bioreactor, and to generate a vortex by stirring to generate bubbles in the culture medium. To accelerate the dissolution of gas in the culture solution by increasing the moving distance and making the contact time between the bubbles and the culture solution as long as possible, and crushing the bubbles coming out of the sparger to make fine bubbles It is possible to promote the dissolution of gas into the culture solution by increasing the contact area with the culture solution.

[0004]

However, the above-mentioned conventional bioreactor has a problem that the gas supply efficiency is poor for the following reasons.

That is, first, a vortex flow is generated by stirring to lengthen the moving distance of bubbles in the culture solution and to lengthen the contact time between the bubbles and the culture solution as much as possible, thereby promoting the dissolution of gas in the culture solution. There is a limit to what can be done. For example, in the case of a culture tank having a depth of 1 m, the residence time of bubbles in the culture solution is only several seconds to 10 seconds, but in such a short time, gas hardly dissolves in the culture solution and Go out.

Further, there is a limit in crushing the bubbles coming out of the sparger and making them into fine bubbles to increase the contact area of the bubbles with the culture solution to accelerate the dissolution of gas into the culture solution. That is, in order to make the bubbles as fine as possible, it is sufficient to increase the stirring speed, but if the stirring speed is increased, the stirring blades will damage the cells. For this reason, the stirring speed is limited so as not to damage the cells, and thus the stirring speed cannot be made too high.

In view of the above problems, in reality, when the cell concentration in the culture medium becomes high, the supply rate of oxygen gas cannot keep up with the respiration rate of the cells, and the growth of the cells stops or the cells die. Is happening. Also,
It is possible to increase the flow rate of oxygen gas in order to increase the supply rate of oxygen gas.However, when the flow rate of oxygen gas is increased in this way, bubbles form in the upper part of the culture solution, and along with these bubbles, the cells of the bioreactor The problem of going out arises.

The present invention has been made in response to such a conventional situation, and the residence time of bubbles in the culture solution can be significantly lengthened, and the gas supply efficiency is greatly improved as compared with the conventional one. It is intended to provide a bioreactor that can be used.

[0009]

[Means for Solving the Problems] That is, a bioreactor according to claim 1 supplies a predetermined tank with a predetermined culture solution and a predetermined gas into the culture solution to generate bubbles of the gas. A gas supply unit and a liquid flow generation unit that forms a liquid flow of the culture liquid in the culture tank in a direction opposite to the moving direction in which the bubbles move by buoyancy and suppresses the movement of the bubbles are provided. It is characterized by

The bioreactor according to claim 2 extends from a culture tank containing a predetermined culture solution to a vicinity of a bottom portion of the culture tank to a vicinity of an upper liquid surface of the culture solution and partitions the culture tank. A partition body arranged, and an upward flow of the culture solution to one side of the culture tank partitioned by the partition body,
Liquid flow generating means for forming a downflow of the culture solution on the other side, and a predetermined gas is supplied into the culture solution on the side where the downflow is formed in the culture tank, and bubbles of this gas are generated. And a gas supply means for controlling the gas supply.

The bioreactor according to claim 3 has a flat plate shape as a whole, and a culture tank containing a predetermined culture solution therein, and extending from the vicinity of the bottom of the culture tank to the vicinity of the upper surface of the culture solution. A partition body that is present so as to partition the inside of the culture tank, and a stirring blade provided at the lower part of the partition body, so that the culture solution is placed on one side of the culture tank that is partitioned by the partition body. An upward flow, a liquid flow generating means for forming a downward flow of the culture solution on the other side, and supplying a predetermined gas into the culture solution on the side where the downward flow is formed in the culture tank,
And a gas supply means for generating gas bubbles.

[0012]

In the bioreactor of the present invention having the above-mentioned structure, the liquid flow generating means forms a liquid flow of the culture liquid in the culture tank in a direction opposite to the moving direction of the bubbles moving by the buoyancy, and Control movement.

As a result, the residence time of the bubbles in the culture solution can be significantly lengthened, and the gas supply efficiency can be greatly improved as compared with the conventional case.

Further, by significantly increasing the residence time of the bubbles in the culture medium, the gas in the bubbles gradually dissolves into the culture medium, and the bubbles become smaller, so that substantially small bubbles were generated. As in the case, the contact area between the gas and the liquid can be increased, and thus the gas supply efficiency can be improved.

Further, since the bubbles are placed in the liquid flow of the culture solution which opposes the direction of movement due to buoyancy, the culture solution flows around the bubbles to promote the dissolution of gas into the culture solution.

Therefore, it is possible to supply a sufficient amount of oxygen, carbon dioxide, etc. to the culture solution at a gas flow rate that can prevent foaming and without damaging cells. Good culture can be performed.

[0017]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of the present invention will be described below with reference to the drawings.

FIG. 1 and FIG. 2 show the construction of a bioreactor suitable for culturing Chlorella etc. as a bioreactor of one embodiment of the present invention. In these figures, 1 indicates a culture tank.

The culture tank 1 is formed of a transparent plate material (in this embodiment, an acrylic plate material) in the shape of a flat-plate container, and constant temperature water is circulated on the outside of the culture tank 1. A constant temperature water tank 2 is provided to maintain a predetermined culture temperature.

In this embodiment, the culture tank 1 has a height (h) of about 500 mm and a width (w) of about 400 mm.
The thickness (t) is about 50 mm, and the thickness (T) of the constant temperature water tank 2 is about 20 mm.

Further, inside the culture tank 1, there is provided a partition plate 4 extending from near the bottom to near the upper liquid surface of the culture solution 3 so as to partition the inside of the culture tank 1 at the center in the thickness direction. A stirring blade 5 is provided below the partition plate 4, and a sparger 6 is provided obliquely above the stirring blade 5.

The stirring blade 5 is configured to be rotated in the direction of the arrow shown by a motor 7 provided outside the culture tank 1. Further, the sparger 6 is a tubular body 6.
a is provided with a plurality of fine holes 6b, and one end thereof has a gas pipe 8 connected to a gas supply source (not shown).
Are connected. The pores 6b of the sparger 6
Are pierced sideways (or downwards) to prevent cells from clogging. Further, the pores 6b have a minute diameter in order to make the generated bubbles as small as possible, and in this embodiment, the diameter is set to 0.8 mm or less.

When culturing Chlorella or the like in the bioreactor of this embodiment having the above-mentioned structure, the culturing is carried out as follows.

That is, a predetermined amount of the culture solution 3 in which a predetermined nutrient source is dissolved is put into the culture tank 1, and the inside of the culture tank 1 is set to a predetermined temperature by the constant temperature water tank 2. Then, while supplying gas such as oxygen and carbon dioxide to the culture solution 3 by the gas pipe 8 and the sparger 6, the stirring blade 5 is rotated by the motor 7 in the direction of the arrow at a predetermined speed so that the inside of the culture tank 1 is fed from both sides. The cells are cultured by irradiating them with light.

At this time, by rotating the stirring blade 5, a liquid flow of the culture solution 3 that rises on the right side of the partition plate 4 in FIG. For this reason,
The bubbles A generated in the culture medium 3 by the gas supplied from the pores 6b of the sparger 6 try to rise due to buoyancy, but are prevented from rising due to the descending liquid flow of the culture medium 3, Will stay for a long time.

As a result, the contact time between the gas and the culture solution 3 becomes longer, the gas dissolves in the culture solution 3, and the gas supply efficiency can be greatly improved. Further, by significantly increasing the residence time of the bubbles in the culture solution 3, the gas in the bubbles gradually dissolves in the culture solution 3 and the bubbles become smaller, so that when substantially small bubbles are generated. Similarly, the contact area between the gas and the liquid can be increased, which can improve the gas supply efficiency. Furthermore, since the bubbles are placed in the liquid flow of the culture solution 3 which is opposed to the moving direction due to the buoyancy, the culture solution 3 flows around the bubbles to promote the dissolution of the gas into the culture solution 3.

Therefore, it is possible to supply a sufficient amount of oxygen, carbon dioxide, etc. into the culture solution at a gas flow rate that can prevent foaming and without damaging cells. Good culture can be performed.

In the case of the present embodiment, the stirring blade 5 is rotated at 180 (rotation / minute), and the flow rate of the liquid flow of the culture medium 3 is set at a linear velocity of 10 c.
If set to about m / sec, bubbles of standard size generated from the pores 6b of the sparger 6 will be in the culture solution 3 for about several minutes.
It was confirmed to stay inside. In addition, when the stirring blade 5 was stopped and the liquid flow of the culture solution 3 was stopped, the residence time of such bubbles in the culture solution 3 was about 1 second.

Further, the bubbles having a size of a certain size or less are caused to flow in the liquid flow of the culture medium 3, rise from the opposite side of the partition plate 4, and are discharged. Further, the bubbles that have become large due to the coalescence of some bubbles are slowly raised in the downward flow of the culture medium 3 and are discharged.

[0030]

As described above, according to the bioreactor of the present invention, the residence time of bubbles in the culture solution can be significantly lengthened, and the gas supply efficiency can be significantly improved as compared with the conventional case. Can be made. This makes it possible to supply a sufficient amount of oxygen, carbon dioxide, etc. into the culture solution at a gas flow rate that can prevent foaming and without damaging cells. Culture can be performed.

[Brief description of drawings]

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

FIG. 2 is a diagram showing a side configuration of the bioreactor of FIG.

[Explanation of symbols]

 1 culture tank 2 constant temperature water tank 3 culture solution 4 partition plate 5 stirring blade 6 sparger 6a pipe body 6b pore 7 motor 8 gas pipe

Claims (3)

[Claims] 1. A culture tank for containing a predetermined culture solution, a gas supply unit for supplying a predetermined gas into the culture solution to generate bubbles of the gas, and a buoyancy of the bubbles in the culture tank. A bioreactor comprising: a liquid flow generating unit that forms a liquid flow of the culture liquid in a direction opposite to the moving direction of the liquid and suppresses the movement of the bubbles. 2. A culture tank containing a predetermined culture solution, and a partitioning body extending from the vicinity of the bottom of the culture tank to the vicinity of the upper surface of the culture solution and arranged so as to partition the inside of the culture tank. , An upward flow of the culture solution on one side of the culture tank partitioned by the partition body, a liquid flow generating means for forming a downward flow of the culture solution on the other side, and the downward flow in the culture tank is A bioreactor comprising: a gas supply means for supplying a predetermined gas into the culture solution on the side where the gas is formed and generating bubbles of the gas. 3. A culture tank having a flat plate shape as a whole and containing a predetermined culture solution therein, and a culture tank extending from the vicinity of the bottom of the culture tank to the vicinity of the upper surface of the culture solution in the culture tank. A partitioning body arranged so as to partition the partition, and an agitating blade disposed below the partitioning body, to the one side of the culture tank partitioned by the partitioning body, the upward flow of the culture solution to the other side. Liquid flow generating means for forming a downward flow of the culture solution, and gas supply for supplying a predetermined gas into the culture solution on the side where the downward flow is formed in the culture tank, and generating gas bubbles of this gas And a bioreactor.