JPH0595778A - Porous separation membrane integrated type incubator equipped with stirrer - Google Patents

Porous separation membrane integrated type incubator equipped with stirrer

Info

Publication number
JPH0595778A
JPH0595778A JP28551291A JP28551291A JPH0595778A JP H0595778 A JPH0595778 A JP H0595778A JP 28551291 A JP28551291 A JP 28551291A JP 28551291 A JP28551291 A JP 28551291A JP H0595778 A JPH0595778 A JP H0595778A
Authority
JP
Japan
Prior art keywords
culture
solution
separation membrane
porous
incubator
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
JP28551291A
Other languages
Japanese (ja)
Other versions
JPH07121216B2 (en
Inventor
Takahiro Suzuki
高広 鈴木
Minoru Kominami
実 小南
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chuo Setsubi Eng Kk
National Institute of Advanced Industrial Science and Technology AIST
Original Assignee
Chuo Setsubi Eng Kk
Agency of Industrial Science and Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chuo Setsubi Eng Kk, Agency of Industrial Science and Technology filed Critical Chuo Setsubi Eng Kk
Priority to JP3285512A priority Critical patent/JPH07121216B2/en
Publication of JPH0595778A publication Critical patent/JPH0595778A/en
Publication of JPH07121216B2 publication Critical patent/JPH07121216B2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/02Stirrer or mobile mixing elements
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M21/00Bioreactors or fermenters specially adapted for specific uses
    • C12M21/18Apparatus specially designed for the use of free, immobilized or carrier-bound enzymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/02Percolation
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/04Filters; Permeable or porous membranes or plates, e.g. dialysis

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Sustainable Development (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

PURPOSE:To obtain the subject apparatus capable of efficiently producing cells at a high density for a long period by equipping a stirred type incubator or a bioreactor for a microorganism, a cell or an immobilized enzyme with a filtering and separating membrane for filtering and separating a culture solution or a reactional solution parallel to the culture or reaction. CONSTITUTION:A stirred type incubator or a stirred type bioreactor is composed of an outer vessel 2 having a culture solution taking out pipe 7 and an aeration pipe 12 and an upper lid 3 equipped with a substrate solution feed pipe 5, a culture solution circulating feed pipe 6 and an aeration pipe 11 and has a stirrer 4 in the interior. A ceramic porous cylinder 1 as a porous separation membrane for filtering and separating a culture solution or a reactional solution is installed in this incubator or bioreactor and its interior is separated into a culturing part or a reactional part and a filtering part by the partition wall (porous cylinder) 1 composed of the porous separation membrane. Thereby, a microorganism, a cell or an immobilized enzyme is filled and cultured or reacted to maintain the cell or immobilized enzyme at a high density in the culture or reactional solution. As a result, the product is continuously produced with a high efficiency.

Description

【発明の詳細な説明】Detailed Description of the Invention

【0001】[0001]

【産業上の利用分野】本発明は、特に培養あるいは反応
とろ過分離を並行して行うのに好適な、撹拌型培養器あ
るいは撹拌型バイオリアクターに多孔質分離膜を装備し
て成る装置に関する。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus comprising a stirring type incubator or a stirring type bioreactor equipped with a porous separation membrane, which is suitable for carrying out culture or reaction and filtration separation in parallel.

【0002】[0002]

【従来の技術】従来、微生物、細胞又は固定化酵素を蔵
する撹拌型培養装置あるいは撹拌型バイオリアクター
と、培養液あるいは反応液のろ過分離装置はそれぞれ独
立して使われていたために、培養装置あるいはバイオリ
アクターから培養液あるいは反応液を回収し、分離装置
へ搬送しなければならなかった。従って、培養あるいは
反応工程と分離工程が回分方式であり、非効率的であっ
た。
2. Description of the Related Art Conventionally, a stirring type culture device or a stirring type bioreactor for storing microorganisms, cells or immobilized enzymes and a filtration and separation device for a culture solution or a reaction solution have been used independently. Alternatively, it was necessary to collect the culture solution or the reaction solution from the bioreactor and transport it to the separation device. Therefore, the culturing or reaction step and the separation step are batch-wise and inefficient.

【0003】一方、僅かに、嫌気発酵工程において塔型
セラミック分離膜内部に細胞を保持し、発酵と培養液の
分離を並行して行う方法があるが、塔内の培養液の撹拌
混合ができないために、基質と細胞の混合状態が不均一
となり、培養速度が低く、細胞密度を高めることが困難
であった。
On the other hand, there is a method of slightly holding the cells inside the tower-type ceramic separation membrane in the anaerobic fermentation process and carrying out the fermentation and the separation of the culture solution in parallel, but it is impossible to stir and mix the culture solution in the tower. Therefore, the mixed state of the substrate and the cells became non-uniform, the culture rate was low, and it was difficult to increase the cell density.

【0004】一方、多量の酸素を必要とする好気性細胞
の場合には、溶存酸素が不足するために膜内部で細胞密
度を高めることができなかった。
On the other hand, in the case of aerobic cells which require a large amount of oxygen, it was not possible to increase the cell density inside the membrane due to lack of dissolved oxygen.

【0005】また、従来の膜による分離ろ過工程は、膜
の細孔内部に微生物、細胞、固定化酵素などが充填し目
詰まりしやすく、多量の分離膜を使用しなければならな
かった。
Further, in the conventional separation and filtration process using a membrane, the inside of the pores of the membrane are easily filled with microorganisms, cells, immobilized enzymes and the like, so that a large amount of separation membranes must be used.

【0006】また、目詰まりした場合には多量の洗浄液
を逆流させることにより膜の再生を行っていたために、
目詰まりした微生物、細胞、固定化酵素などはこの洗浄
工程により流失してしまい、長期連続運転が困難であっ
た。
Further, when clogging occurs, the membrane is regenerated by back-flowing a large amount of cleaning liquid.
Clogged microorganisms, cells, immobilized enzymes, etc. were washed away by this washing process, making long-term continuous operation difficult.

【0007】[0007]

【発明が解決しようとする課題】本発明は、このような
事情の下、培養器やバイオリアクター中に微生物、細胞
又は固定化酵素を長期にわたって成育しあるいは保持す
るとともに、多孔質分離膜により培養液あるいは反応液
と微生物、細胞又は固定化酵素を連続的に、かつ効率的
に分離する装置を提供することを目的としてなされたも
のである。
Under the above circumstances, the present invention allows microorganisms, cells, or immobilized enzymes to grow or be retained for a long period of time in a culture vessel or bioreactor and to be cultured by a porous separation membrane. The object of the present invention is to provide an apparatus for continuously and efficiently separating a liquid or a reaction liquid from a microorganism, a cell or an immobilized enzyme.

【0008】[0008]

【課題を解決するための手段】本発明者らは、前記の好
ましい性質を有する装置を開発すべく鋭意研究を重ねた
結果、撹拌型培養器あるいは撹拌型バイオリアクターに
多孔質分離膜を装備させることにより、その目的を達成
しうることを見出し、この知見に基づいて本発明を完成
するに至った。
Means for Solving the Problems As a result of intensive studies to develop an apparatus having the above-mentioned preferable properties, the present inventors have installed a stirring type incubator or a stirring type bioreactor with a porous separation membrane. As a result, they have found that the object can be achieved, and have completed the present invention based on this finding.

【0009】すなわち、本発明は、微生物、細胞又は固
定化酵素の撹拌型培養器あるいは撹拌型バイオリアクタ
ーに、培養あるいは反応と並行して培養液あるいは反応
液のろ過分離を行うための多孔質分離膜を装備して成る
装置を提供するものである。
That is, the present invention provides a porous separation for performing filtration separation of a culture solution or a reaction solution in parallel with a culture or a reaction in a stirring type incubator or a stirring type bioreactor for microorganisms, cells or immobilized enzymes. A device provided with a membrane is provided.

【0010】本発明に用いる多孔質分離膜については特
に制限はなく、微生物、細胞又は固定化酵素の撹拌型培
養器あるいは撹拌型バイオリアクターによる培養あるい
は反応で得られた培養液あるいは反応液を微生物、細胞
又は固定化酵素から分離ろ過する機能を有するものであ
ればよく、例えば多孔質セラミック膜、多孔質ガラス
膜、多孔質有機高分子膜、金属繊維編織体、不織布など
を用いることができる。これらの中で特にセラミック多
孔質膜が好適である。この微生物や細胞や固定化酵素に
ついては特に制限はないが、例えば酵母、大腸菌、放線
菌、固定化グルコースイソメラーゼなどが挙げられる。
The porous separation membrane used in the present invention is not particularly limited, and a culture solution or reaction solution obtained by culturing or reacting a microorganism, a cell or an immobilized enzyme in a stirring type incubator or a stirring type bioreactor is used as a microorganism. As long as it has a function of separating and filtering from cells or immobilized enzyme, for example, a porous ceramic membrane, a porous glass membrane, a porous organic polymer membrane, a metal fiber knitted body, a non-woven fabric or the like can be used. Of these, a ceramic porous membrane is particularly suitable. The microorganisms, cells and immobilized enzymes are not particularly limited, but examples thereof include yeast, Escherichia coli, actinomycetes and immobilized glucose isomerase.

【0011】また、撹拌混合方式としては従来公知のも
の、例えば撹拌軸、撹拌棒、撹拌板、撹拌羽根、撹拌磁
石、通気管、液循環ポンプなどによる方式を用いること
ができるが、これらの中で撹拌羽根による方式が好適で
ある。
As the stirring and mixing method, a conventionally known method such as a stirring shaft, a stirring rod, a stirring plate, a stirring blade, a stirring magnet, a ventilation pipe, and a liquid circulation pump can be used. Therefore, a method using a stirring blade is preferable.

【0012】多孔質分離膜の装備構造としては、有利に
は前記培養器あるいはバイオリアクター内部を微生物、
細胞又は固定化酵素の保持部とし、外部を培養ろ液部又
は反応ろ液部に分割するように隔壁構造とした二重構造
のものが好ましい。この隔壁構造の場合、前記保持部に
撹拌混合機能を備えさせるようにする。この多孔質分離
膜を隔壁とした二重構造の装置を用いれば、前記培養液
あるいは反応液を撹拌しながらろ過分離工程を進めるこ
とができ、撹拌により微生物、細胞又は固定化酵素が多
孔質分離膜の孔内に侵入するのを防ぐことが可能になる
ことから、多孔質分離膜の目詰まりを防止し、長時間高
いろ過効率が得られる。
As the equipment structure of the porous separation membrane, it is preferable that the inside of the incubator or the bioreactor is a microorganism,
It is preferable that the cell or immobilized enzyme has a double structure having a partition structure so as to divide the outside into a culture filtrate part or a reaction filtrate part as a holding part for the enzyme. In the case of this partition structure, the holding part is provided with a stirring and mixing function. By using a device having a double structure with this porous separation membrane as a partition, the filtration separation step can be carried out while stirring the culture solution or reaction solution, and the microorganisms, cells or immobilized enzyme can be separated by the porous separation by stirring. Since it is possible to prevent the infiltration into the pores of the membrane, it is possible to prevent clogging of the porous separation membrane and obtain high filtration efficiency for a long time.

【0013】さらに、前記二重構造の装置においては、
通気管を多孔質分離膜の内側の前記保持部と多孔質分離
膜の外側の前記ろ液部の両者に導入し、両者の通気流量
を調節することにより多孔質分離膜内外の圧力差を調節
し、多孔質膜の目詰まりを防ぐこともできる。
Further, in the device having the double structure,
A ventilation pipe is introduced into both the holding part inside the porous separation membrane and the filtrate part outside the porous separation membrane, and the pressure difference between the inside and outside of the porous separation membrane is adjusted by adjusting the ventilation flow rate of both. However, it is also possible to prevent clogging of the porous membrane.

【0014】また、撹拌又は通気撹拌しながら培養液の
ろ過分離工程を並行して行うために、嫌気性細胞のみな
らず、好気性細胞を良好に成育せしめ、培養器内の細胞
密度を極限値まで高めることができる。従って、有用物
質が細胞内部に生産される場合には、前記保持部から余
剰の培養液が連続的に分離されることにより、生産手段
である細胞を極限高密度になるまで培養でき、培養効率
を高めることができる。
Further, since the filtration and separation steps of the culture solution are performed in parallel with stirring or aeration stirring, not only anaerobic cells but also aerobic cells can be well grown, and the cell density in the incubator is set to the maximum value. Can be increased up to. Therefore, when the useful substance is produced inside the cells, the excess culture solution is continuously separated from the holding part, whereby the cells as a production means can be cultured to an extremely high density, and the culture efficiency is improved. Can be increased.

【0015】また、本発明による培養器やバイオリアク
ターを用いれば、微生物や細胞や酵素が培養液や反応液
中に分泌しあるいは産生する有用物質を連続的に回収す
ることができる。細胞は培養液内部に残るため、長時間
高い細胞密度を維持することができ、連続的に高効率で
目的物質を生産しうる。
Further, by using the incubator or bioreactor according to the present invention, useful substances secreted or produced by microorganisms, cells or enzymes in the culture solution or reaction solution can be continuously recovered. Since the cells remain inside the culture medium, the high cell density can be maintained for a long time, and the target substance can be continuously and efficiently produced.

【0016】また、培地中に微生物や細胞の成育阻害物
質が生成する場合にも、常に阻害物質を多孔質分離膜に
よるろ過分離で除去し、新鮮培地を供給することができ
るため、細胞の生育を促進することができる。
Further, even when microorganisms or cell growth inhibitory substances are produced in the medium, the inhibitory substances can always be removed by filtration separation through a porous separation membrane, and a fresh medium can be supplied, so that cell growth is prevented. Can be promoted.

【0017】さらに、本発明においては、通気圧調節に
より、間欠的にろ液を逆流させ目詰まりを解消し、多孔
質膜を交換することなく長期間高い効率で培養液あるい
は反応液の分離ろ過を行うことができる。
Further, in the present invention, the ventilation pressure is adjusted to intermittently cause the filtrate to flow backward to eliminate clogging, and the filtration or separation of the culture solution or the reaction solution can be performed with high efficiency for a long period without replacing the porous membrane. It can be performed.

【0018】[0018]

【発明の効果】本発明の装置によれば、培養器あるいは
バイオリアクター内に微生物、細胞又は固定化酵素を保
持したまま、撹拌あるいは通気撹拌と、培養液あるいは
反応液と、微生物、細胞又は固定化酵素との分離を効率
的に且つ連続的に行うことができる。さらに、培養液中
の細胞を長期的に極限高密度に維持し、生成物を連続的
に高い効率で生産しうる。
EFFECTS OF THE INVENTION According to the apparatus of the present invention, stirring or aeration stirring is carried out while the microorganism, cell or immobilized enzyme is held in the incubator or bioreactor, and the culture solution or reaction solution is mixed with the microorganism, cell or immobilization. It is possible to efficiently and continuously carry out the separation from the enzyme. Furthermore, the cells in the culture medium can be maintained at an extremely high density for a long period of time, and the product can be continuously produced with high efficiency.

【0019】[0019]

【実施例】次に、実施例により本発明をさらに詳細に説
明するが、本発明はこれらの例によってなんら限定され
るものではない。
EXAMPLES The present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

【0020】実施例1 多孔質セラミック分離膜からなる内筒の内側に撹拌羽
根、該内筒の内側と外側の両方に通気管を装備した培養
器による、酵母菌の培養について説明する。
Example 1 Cultivation of yeast by an incubator equipped with a stirring blade inside an inner cylinder made of a porous ceramic separation membrane and a ventilation tube both inside and outside the inner cylinder will be described.

【0021】図1に示す培養器を用いた。図1におい
て、1は平均細孔径5μmのセラミック多孔質分離膜か
らなる有底円筒体(以下、セラミック多孔質筒という)
であり、それと同心状に十分な空間をもたせて外槽2が
設けられ、それらは気密性を保持するために互いに上部
で接合されるとともに、それらの上端部は上蓋3と接合
されている。上蓋の中心部から撹拌軸がセラミック多孔
質筒内に垂設され、撹拌軸には撹拌羽根4…が付設され
ている。
The incubator shown in FIG. 1 was used. In FIG. 1, reference numeral 1 denotes a bottomed cylindrical body composed of a ceramic porous separation membrane having an average pore diameter of 5 μm (hereinafter referred to as a ceramic porous cylinder).
The outer tub 2 is provided concentrically with it and has a sufficient space. The outer tubs 2 are joined to each other at the top to maintain airtightness, and their upper ends are joined to the upper lid 3. A stirring shaft is vertically provided in the ceramic porous cylinder from the central portion of the upper lid, and stirring blades 4 are attached to the stirring shaft.

【0022】上蓋3には基質液供給管5、培養液循環供
給管6及び通気管11がセラミック多孔質筒内へと配管
されているとともに、pH電極、溶存酸素(以下DOと
いう)電極、温度電極、液面電極(いずれも図示せず)
が取り付けられている。これら電極は外槽2に取り付け
てもよい。外槽2には培養液抜き出し管7及び通気管1
2が配管されている。抜き出された培養液は切り替え弁
8により取り出し管9側あるいは培養液循環供給管6側
へ切り替えられ、培養液循環供給管6側へ循環される培
養液は培養液循環ポンプ10により送給される。各通気
管への通気は流量調節弁13…を介して行われる。ま
た、セラミック多孔質筒上部を予め培養液面よりも低い
ところまで被覆することにより、内外部通気調節により
圧力差を生じさせ、ろ液を逆流させることにより目詰ま
りの解消が行われる。
A substrate liquid supply pipe 5, a culture liquid circulation supply pipe 6 and a ventilation pipe 11 are piped into the ceramic porous cylinder on the upper lid 3, and a pH electrode, a dissolved oxygen (hereinafter referred to as DO) electrode, and a temperature are provided. Electrodes, liquid level electrodes (neither shown)
Is attached. These electrodes may be attached to the outer tank 2. The outer tank 2 has a culture solution extraction tube 7 and a ventilation tube 1
2 is piped. The extracted culture fluid is switched to the take-out pipe 9 side or the culture fluid circulation supply pipe 6 side by the switching valve 8, and the culture fluid circulated to the culture fluid circulation supply pipe 6 side is fed by the culture fluid circulation pump 10. It Ventilation to each ventilation pipe is performed via the flow rate control valves 13. Further, by covering the upper part of the ceramic porous cylinder to a position lower than the culture liquid surface in advance, a pressure difference is generated by adjusting the inside / outside ventilation, and the filtrate is caused to flow backward to eliminate the clogging.

【0023】撹拌羽根の回転速度は毎分1000回転を
超えない回転数の範囲で上部撹拌駆動式により調節し
た。通気管からは、酸素と空気の混合ガスを毎分3lを
超えない流量で供給した。培養液中のDO濃度は、撹拌
羽根の回転速度と通気酸素分圧の調節により、常に酵母
菌の生育最適条件を維持しうるように制御した。
The rotation speed of the stirring blade was adjusted by the upper stirring drive system within a rotation speed range of not more than 1000 rotations per minute. From the ventilation tube, a mixed gas of oxygen and air was supplied at a flow rate not exceeding 3 l / min. The DO concentration in the culture broth was controlled by adjusting the rotating speed of the stirring blade and the partial pressure of aerated oxygen so that the optimum conditions for yeast growth could be maintained at all times.

【0024】この培養器のセラミック多孔質筒内部で酵
母菌を通気撹拌しながら培養した。10重量%グルコー
スと5重量%酵母エキス粉末を含む培地に酵母菌を接種
し、30℃、pH5に維持して通気撹拌培養した。グル
コースが欠乏した時点でDO濃度が上昇する現象を利用
したDOスタット法により、20重量%のグルコースを
含む基質溶液をポンプで自動供給した。このとき同時に
供給液と同じ流量でろ過液を抜き取ったところ、ろ液中
にはグルコースがほとんど検出されなかった。間欠的に
基質供給と、培養液ろ過を繰り返し行うことにより、培
養5日目に培養液中の菌体濃度が乾燥基準で15重量%
に達した。
The yeast was cultivated inside the ceramic porous cylinder of this incubator while aerating and stirring. Yeast was inoculated into a medium containing 10% by weight glucose and 5% by weight yeast extract powder, and the mixture was maintained at 30 ° C. and pH 5 and cultured with aeration and stirring. A substrate solution containing 20% by weight of glucose was automatically supplied by a pump by the DO stat method utilizing the phenomenon that the DO concentration rises when glucose is deficient. At this time, when the filtrate was withdrawn at the same flow rate as the supply liquid, glucose was hardly detected in the filtrate. By intermittently supplying the substrate and repeatedly filtering the culture solution, the cell concentration in the culture solution on the 5th day of culture was 15% by weight on a dry basis.
Reached

【0025】実施例2 間欠的に(1時間毎に)調節弁13の切替えを行い、一
時的に(10分間)セラミック多孔質筒の内側の通気を
止め外側から通気することにより、セラミック多孔質筒
内外の圧力切替えを行い、50ml/分の培養液をセラ
ミック多孔質筒の外から内へ圧入させたこと以外は、実
施例1と全く同様に実施したところ、培地交換速度が早
くなることによって、菌体濃度が速く上昇し、培養5日
目に菌体濃度が乾燥基準で18重量%に達した。
Example 2 The control valve 13 is switched intermittently (every 1 hour), and the ventilation inside the ceramic porous cylinder is stopped temporarily (for 10 minutes) to vent the air from the outside, whereby the ceramic porous The pressure was switched between the inside and outside of the cylinder, and 50 ml / min of the culture solution was pressed into the ceramic porous cylinder from the outside to the inside, and the same procedure as in Example 1 was carried out. The cell concentration rapidly increased, and the cell concentration reached 18% by weight on the dry basis on the 5th day of culture.

【0026】比較例1 実施例1の培養器に代えてそれからセラミック多孔質筒
を除外した構造の培養器を用いたこと以外は、実施例1
と全く同様に実施したところ、培養5日目の培養液中の
菌体濃度は乾燥基準で1重量%以下にすぎなかった。
Comparative Example 1 Example 1 was repeated except that the incubator of Example 1 was replaced with an incubator having a structure in which a ceramic porous tube was omitted.
When carried out exactly in the same manner as above, the cell concentration in the culture medium on the 5th day of culture was only 1% by weight or less on a dry basis.

【0027】比較例2 撹拌を行わなかったこと以外は実施例1と全く同様に実
施したところ、培養5日目の培養液中の菌体濃度は乾燥
基準で2重量%にすぎなかった。
Comparative Example 2 The same procedure as in Example 1 was carried out except that stirring was not carried out. As a result, the cell concentration in the culture solution on the 5th day of culture was only 2% by weight on a dry basis.

【図面の簡単な説明】[Brief description of drawings]

【図1】 培養器の略解図。FIG. 1 is a schematic diagram of an incubator.

【符号の説明】[Explanation of symbols]

1 セラミック多孔質筒 2 外槽 3 上蓋 4 撹拌羽根 5 基質液供給管 6 培養液循環供給管 7 培養液抜き出し管 8 切り替え弁 9 取り出し管 10 培養液循環ポンプ 11,12 通気管 13 流量調節弁 1 Ceramic Porous Cylinder 2 Outer Tank 3 Upper Lid 4 Stirring Blade 5 Substrate Liquid Supply Pipe 6 Culture Liquid Circulation Supply Pipe 7 Culture Liquid Extraction Pipe 8 Switching Valve 9 Extraction Pipe 10 Culture Liquid Circulation Pump 11, 12 Vent Pipe 13 Flow Control Valve

Claims (3)

【特許請求の範囲】[Claims] 【請求項1】 微生物、細胞又は固定化酵素の撹拌型培
養器あるいは撹拌型バイオリアクターに、培養あるいは
反応と並行して培養液あるいは反応液のろ過分離を行う
ための多孔質分離膜を装備して成る装置。
1. A stirring type incubator or a stirring type bioreactor for microorganisms, cells or immobilized enzymes is equipped with a porous separation membrane for filtering and separating a culture solution or a reaction solution in parallel with culture or reaction. A device consisting of
【請求項2】 微生物、細胞又は固定化酵素の撹拌型培
養器あるいは撹拌型バイオリアクターの内部を多孔質分
離膜からなる隔壁により培養部あるいは反応部とろ液部
に分離したことを特徴とする装置。
2. An apparatus characterized in that the inside of a stirring type incubator or a stirring type bioreactor for microorganisms, cells or immobilized enzymes is separated into a culture section or a reaction section and a filtrate section by a partition wall made of a porous separation membrane. ..
【請求項3】 通気による圧力差を利用して多孔質分離
膜の目詰まりを解消することを特徴とする請求項2記載
の装置。
3. The apparatus according to claim 2, wherein clogging of the porous separation membrane is eliminated by utilizing a pressure difference due to ventilation.
JP3285512A 1991-10-07 1991-10-07 Stirred bioreactor and incubator Expired - Lifetime JPH07121216B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP3285512A JPH07121216B2 (en) 1991-10-07 1991-10-07 Stirred bioreactor and incubator

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Application Number Priority Date Filing Date Title
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JPH0595778A true JPH0595778A (en) 1993-04-20
JPH07121216B2 JPH07121216B2 (en) 1995-12-25

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