JPH06102014B2 - Apparatus for aerobic culture of cells and control method thereof - Google Patents
Apparatus for aerobic culture of cells and control method thereofInfo
- Publication number
- JPH06102014B2 JPH06102014B2 JP62240722A JP24072287A JPH06102014B2 JP H06102014 B2 JPH06102014 B2 JP H06102014B2 JP 62240722 A JP62240722 A JP 62240722A JP 24072287 A JP24072287 A JP 24072287A JP H06102014 B2 JPH06102014 B2 JP H06102014B2
- Authority
- JP
- Japan
- Prior art keywords
- air
- oxygen concentration
- dissolved oxygen
- culture
- spargers
- 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.)
- Expired - Lifetime
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、培養プラント等の培養槽に係り、特に、動物
細胞，植物細胞等の細胞を好気的に培養する際の最適溶
存酸素濃度を制御するのに好適な培養装置及びその制御
方法に関するものである。Description: TECHNICAL FIELD The present invention relates to a culture tank such as a culture plant, and particularly to an optimum dissolved oxygen concentration when aerobically culturing cells such as animal cells and plant cells. The present invention relates to a culture device suitable for controlling the culture and a control method thereof.
従来の装置は、特公昭60−18390号に記載のように、細
胞を好気的に培養する際に培養液の溶存酸素濃度を設定
値と比較し、溶存酸素濃度が設定値より低下した場合
は、第１段階として攪拌機回転数を上げ、攪拌機回転数
が設定上限値になった場合は第２段階として通気ガス中
の酸素分圧を上げ、通気ガス中の酸素分圧を設定上限値
になった場合は第３段階として通気量を上げ、逆に培養
液の溶存酸素濃度が設定値より高い場合は、第１段階と
して攪拌機回転数を下げ、攪拌機回転数が設定下限値に
なった場合は第２段階として通気ガス中の酸素分圧を下
げ、通気ガス中の酸素分圧を設定下限値になった場合は
第３段階として通気量を下げることにより、細胞の好気
的培養装置及びその制御方法を形成し用いていた。As described in JP-B-60-18390, the conventional device compares the dissolved oxygen concentration of the culture solution with a set value when aerobically culturing cells, and when the dissolved oxygen concentration is lower than the set value. The first step is to increase the agitator rotation speed, and if the agitator rotation speed reaches the set upper limit value, the second step is to increase the oxygen partial pressure in the aeration gas to set the oxygen partial pressure in the aeration gas to the set upper limit value. If the dissolved oxygen concentration in the culture solution is higher than the set value, the aeration rate is increased as the third step, and if the agitator rotation speed is decreased and the agitator rotation speed reaches the set lower limit value as the first step. As a second step, the oxygen partial pressure in the aeration gas is reduced, and when the oxygen partial pressure in the aeration gas reaches the set lower limit value, the aeration amount is reduced as a third step, so that The control method was formed and used.
上記従来技術は、制御パラメーターやエアー供給量の点
について配慮がされておらず、制御パラメーターが多い
ためにシステムが複雑で大きくなり、高価になること
や、培養液自体の粘度が高粘度になった場合エアースパ
ージャーの穴径が一定で小さい場合に、エアーの吹出圧
力の損失が大きくなり、エアー供給量と圧力とが低下す
るという問題があった。The above-mentioned conventional technology does not consider the control parameters and the amount of air supply.Since there are many control parameters, the system becomes complicated and large, the cost becomes high, and the viscosity of the culture solution itself becomes high. In this case, when the hole diameter of the air sparger is constant and small, there is a problem that the loss of the air blowing pressure becomes large and the air supply amount and the pressure decrease.
本発明の目的は、培養初期から末期までの広い範囲に亘
り、培養液中の溶存酸素濃度を適正に制御することによ
り、安価で簡単な細胞の好気的培養装置及びその制御方
法を提供することにある。An object of the present invention is to provide an inexpensive and simple aerobic cell culture apparatus and a control method thereof by appropriately controlling the dissolved oxygen concentration in a culture solution over a wide range from the initial stage to the final stage of culture. Especially.
上記目的は、微小穴径をもつエアースパージャーと、穴
径の大きいエアースパージャーと、溶存酸素濃度センサ
ーとを培養槽に組み込み、培養液の溶存酸素濃度の変化
量に応じ、前記エアースパージャーへのエアー供給ルー
トをマイクロコンピュータで切換えることにより、最適
培養条件を溶存酸素濃度センサーの検出値で制御するこ
とにより、達成される。The above-mentioned purpose is to incorporate an air sparger having a small hole diameter, an air sparger having a large hole diameter, and a dissolved oxygen concentration sensor into a culture tank, and to change the dissolved oxygen concentration of a culture solution according to the air sparger. This is achieved by controlling the optimum culture conditions with the value detected by the dissolved oxygen concentration sensor by switching the air supply route to the micro computer.
培養槽内に組込んだ、微小穴径をもつエアースパージャ
ーと、穴径の大きいエアースパージャーとに溶存酸素濃
度センサーおよび培養シーケンスを組込んだマイクロコ
ンピュータからの信号により、エアーの供給を自動切換
弁で行ない、かつ流量調節も行なう。Automatic air supply by a signal from a microcomputer that incorporates a dissolved oxygen concentration sensor and a culture sequence into an air sparger with a small hole diameter and an air sparger with a large hole diameter that are installed in the culture tank. The changeover valve is used and the flow rate is adjusted.
例えば、菌体増殖期においては、培養液への多量の酸素
吸収が要求されるが、その時は微小穴径のエアースパー
ジャーによりエアーの供給を行なって酸素吸収速度を稼
ぎ、菌体からの有用物質分泌期のように比較的要求され
る酸素量が少く、分泌物質により培養液が高粘度となる
場合は、穴径の大きいエアースパージャーに切換え、培
養初期より末期までの広範囲に亘り、適切なエアースパ
ージャーを自動選択しながら、最適な培養を行なうこと
が可能となる。For example, in the bacterial cell growth phase, a large amount of oxygen is required to be absorbed into the culture solution. At that time, air is supplied by an air sparger having a micropore diameter to increase the oxygen absorption rate, which is useful from bacterial cells. When the amount of oxygen required is relatively small, such as during the substance secretory period, and the culture fluid becomes highly viscous due to secretory substances, switch to an air sparger with a large hole diameter, which is suitable over a wide range from the initial stage to the final stage of the culture. Optimum culture can be performed while automatically selecting the appropriate air sparger.
以下、本発明の一実施例を第１図および第２図により説
明する。An embodiment of the present invention will be described below with reference to FIGS. 1 and 2.
図において、装置の構成は、培養槽本体１と、エアー供
給用のエアースパージャー２（微小穴径をもつもの）
と、エアースパージャー３（穴径の大きいノズル型のエ
アースパージャー）と、これらへのエアー供給ルートの
切換用の自動切換弁6,7,供給エアーの流量調節のための
エアー流量計8,エアー流量調節弁9,供給エアー除菌用フ
ィルター10とからなるエアー供給系統と、溶存酸素濃度
センサー4,マイクロコンピュータ５とからなる制御系と
の２系統から成る。マイクロコンピュータ５は、予め培
養過程と必要な溶存酸素濃度との関連をまとめたソフト
によりシーケンス制御ができるように構成している。な
おエアースパージャー2,3への、穴明け位置や穴径の大
きさやノズル取付等は適宜設計変更できるので、本実施
例に限定するものではない。また、エアースパージャー
2,3の数量も本実施例では二組であるが、必要なエアー
量に応じて、増設するものとする。更に溶存酸素濃度セ
ンサー４の取付位置や数量も適宜設計変更できるので、
本実施例に限定するものではない。In the figure, the structure of the apparatus is shown as a culture tank body 1 and an air sparger 2 for supplying air (having a minute hole diameter).
, Air sparger 3 (nozzle type air sparger with a large hole diameter), automatic switching valves 6, 7 for switching the air supply route to these, air flow meter 8, for adjusting the flow rate of the supply air, It is composed of two systems, an air supply system consisting of an air flow rate control valve 9 and a supply air sterilization filter 10, and a control system consisting of a dissolved oxygen concentration sensor 4 and a microcomputer 5. The microcomputer 5 is configured so that sequence control can be performed by software that summarizes the relationship between the culture process and the required dissolved oxygen concentration in advance. It should be noted that the positions of the holes, the diameter of the holes, the nozzle attachment, and the like for the air spargers 2 and 3 can be changed in design as appropriate, and thus the present invention is not limited to this embodiment. Also, air sparger
The numbers of 2 and 3 are two sets in this embodiment, but the number is increased according to the required air amount. Furthermore, the design of the mounting position and quantity of the dissolved oxygen concentration sensor 4 can be changed as appropriate.
The present invention is not limited to this example.
以上の構成において、溶存酸素濃度センサー４より、培
養中の培養液中溶存酸素濃度を検出しその信号をマイク
ロコンピュータ５に送る。In the above configuration, the dissolved oxygen concentration sensor 4 detects the dissolved oxygen concentration in the culture medium during the culture and sends the signal to the microcomputer 5.
この時、培養過程のうち、菌体増殖期等で単位時間当り
の酸素吸収量が大である場合は、マイクロコンピュータ
５から自動切換弁６およびエアー流量調節弁９へ信号を
送り、酸素吸収速度を増加させるため、自動切換弁６を
開き、エアースパージャー２よりエアーの供給を行な
い、溶存酸素濃度を制御する。At this time, when the oxygen absorption amount per unit time is large during the cell growth phase in the culture process, a signal is sent from the microcomputer 5 to the automatic switching valve 6 and the air flow rate control valve 9 to determine the oxygen absorption rate. In order to increase the temperature, the automatic switching valve 6 is opened and air is supplied from the air sparger 2 to control the dissolved oxygen concentration.
また、菌体からの有用物質分泌期のように、比較的要求
される酸素量が少く、分泌物質により培養液が高粘度と
なる場合は、自動切換弁７を開きエアースパージャー３
に切換え、溶存酸素濃度を制御する。更に必要に応じて
自動切換弁6,7を開きエアースパージャー2,3の両方を使
用して溶存酸素濃度を制御することも可能である。Further, when the amount of oxygen required is relatively small and the culture solution becomes highly viscous due to secreted substances, such as during the useful substance secreting period from bacterial cells, the automatic switching valve 7 is opened and the air sparger 3 is opened.
To control the dissolved oxygen concentration. Further, it is possible to open the automatic switching valves 6 and 7 as needed and use both of the air spargers 2 and 3 to control the dissolved oxygen concentration.
本実施例によれば、培養初期より末期までの広範囲に亘
り、適切なエアースパージャーを自動選択しながら最適
な培養を行なえる効果がある。According to this example, there is an effect that optimum culture can be performed while automatically selecting an appropriate air sparger over a wide range from the initial stage to the final stage of the culture.
本発明によれば、細胞を好気的に培養する際に、培養初
期より末期までの広範囲に亘り適切なエアースパージャ
ーを自動選択しながら最適な培養を行なえる細胞の好気
的培養装置及びその制御方法が安価で簡単に構成できる
効果がある。According to the present invention, when aerobically culturing cells, an aerobic culturing device for cells capable of performing optimal culturing while automatically selecting an appropriate air sparger over a wide range from the initial stage to the final stage of culturing, and The control method is inexpensive and can be easily configured.
第１図は本発明の一実施例の培養装置及びその制御方法
の構成図、第２図は第１図のエアースパージャー部の詳
細図である。 １……培養槽本体、２……エアースパージャー、３……
エアースパージャー、４……溶存酸素濃度センサー、５
……マイクロコンピュータ、６……自動切換弁、７……
自動切換弁、８……エアー流量計、９……エアー流量調
節弁、10……エアー除菌フィルターFIG. 1 is a block diagram of a culture device and a control method thereof according to an embodiment of the present invention, and FIG. 2 is a detailed view of the air sparger portion of FIG. 1 ... Incubator body, 2 ... Air sparger, 3 ...
Air sparger, 4 ... Dissolved oxygen concentration sensor, 5
...... Microcomputer, 6 …… Automatic switching valve, 7 ……
Automatic switching valve, 8 ... Air flow meter, 9 ... Air flow control valve, 10 ... Air sanitizing filter
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｃ１２Ｎ 5/02 8412−4Ｂ (72)発明者 園田 浩 山口県下松市大字東豊井794番地 株式会 社日立製作所笠戸工場内 (56)参考文献 特公 昭62−14270（ＪＰ，Ｂ２)─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Internal reference number FI Technical display location C12N 5/02 8412-4B (72) Inventor Hiroshi Sonoda 794 Higashitoyo, Higashitoyo, Yamaguchi Prefecture Stock Association Company Hitachi Ltd. Kasado Plant (56) References Japanese Patent Publication Sho 62-14270 (JP, B2)
Claims (3)
径の大きいエアースパージャーの両エアースパージャー
を有する培養槽と、前記両エアースパージャーへのエア
ー供給用の配管と、前記培養槽内の培養液の溶存酸素濃
度を計る溶存酸素濃度センサーと、前記溶存酸素濃度を
コントロールするためのプログラムを組込んだマイクロ
コンピュータと、前記両エアースパージャーへの配管上
に設けたエアー流量調節弁と、前記溶存酸素濃度が設定
値より低下した場合は前記微小穴径を有するエアースパ
ージャーでエアーの供給を行ない、逆に前記溶存酸素濃
度が設定値より高い場合は前記穴径の大きいエアースパ
ージャーでエアーの供給を行なうよう前記両エアースパ
ージャーへのエアー供給を切り換える自動切換弁とを設
け、前記溶存酸素濃度センサーで計られる溶存酸素濃度
の出力を、前記マイクロコンピュータを介して、前記エ
アー流量調節弁と前記自動切換弁に各々連絡したことを
特徴とする細胞の好気的培養装置。1. A culture tank having both air spargers having a small hole diameter and an air sparger having a large hole diameter, a pipe for supplying air to the both air spargers, and the inside of the culture tank. A dissolved oxygen concentration sensor for measuring the dissolved oxygen concentration of the culture solution, a microcomputer incorporating a program for controlling the dissolved oxygen concentration, and an air flow control valve provided on the pipes to both the air spargers When the dissolved oxygen concentration is lower than a set value, air is supplied by an air sparger having the fine hole diameter, and conversely, when the dissolved oxygen concentration is higher than the set value, the air sparger having a large hole diameter is used. An automatic switching valve that switches the air supply to both air spargers to supply air to the The output of the dissolved oxygen concentration measured in degrees sensor via said microcomputer, said air flow rate control valve and the aerobic culture apparatus of cells, characterized in that respectively contact the automatic switching valve.
て、 培養槽内の培養液の溶存酸素濃度を溶存酸素濃度センサ
ーで検出し、該検出結果を予め前記溶存酸素濃度をコン
トロールするためのプログラムを組込んだマイクロコン
ピュータで演算処理し、前記溶存酸素濃度が設定値より
低下した場合は前記微小穴径を有するエアースパージャ
ーでエアーの供給を行ない、逆に前記溶存酸素濃度が設
定値より高い場合は前記穴径の大きいエアースパージャ
ーでエアーの供給を行なうよう前記両エアースパージャ
ーを制御することを特徴とする細胞の好気的培養方法。2. A method for controlling an aerobic culture apparatus for cells, comprising detecting a dissolved oxygen concentration of a culture solution in a culture tank with a dissolved oxygen concentration sensor, and detecting the detection result in advance to control the dissolved oxygen concentration. When the dissolved oxygen concentration is lower than the set value, it is supplied with air by an air sparger having the fine hole diameter, and on the contrary, the dissolved oxygen concentration is lower than the set value. An aerobic culturing method for cells, which comprises controlling both air spargers so that air is supplied by the air spargers having the large hole diameters when the height is high.
は、前記両エアースパージャーを同時に用いることを特
徴とする細胞の好気的培養方法。3. A method for aerobic culturing cells according to claim 2, wherein the control uses both of the air spargers at the same time.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62240722A JPH06102014B2 (en) | 1987-09-28 | 1987-09-28 | Apparatus for aerobic culture of cells and control method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62240722A JPH06102014B2 (en) | 1987-09-28 | 1987-09-28 | Apparatus for aerobic culture of cells and control method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6486867A JPS6486867A (en) | 1989-03-31 |
| JPH06102014B2 true JPH06102014B2 (en) | 1994-12-14 |
Family
ID=17063728
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62240722A Expired - Lifetime JPH06102014B2 (en) | 1987-09-28 | 1987-09-28 | Apparatus for aerobic culture of cells and control method thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06102014B2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0773492B2 (en) * | 1989-12-25 | 1995-08-09 | 株式会社日立製作所 | Aeration culture method of biological cells, aeration gas ejection device and aeration culture device |
| JPH06153910A (en) * | 1992-11-27 | 1994-06-03 | Tabai Espec Corp | Method for culture and device therefor |
| JP2006034235A (en) * | 2004-07-29 | 2006-02-09 | Fukuoka Prefecture Shoyu Jozo Kyodo Kumiai | Culture apparatus of polymer compound-producing microorganism and culture method |
| WO2008088371A2 (en) | 2006-06-16 | 2008-07-24 | Xcellerex, Inc. | Gas delivery configurations, foam control systems, and bag molding methods and articles for collapsible bag vessels and bioreactors |
| DE102009052670B4 (en) * | 2009-11-12 | 2017-10-05 | Sartorius Stedim Biotech Gmbh | Fumigation device for bioreactors |
| DE102010046989B4 (en) * | 2010-09-30 | 2015-07-30 | Sartorius Stedim Biotech Gmbh | Fumigation device for bioreactors |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6214270A (en) * | 1985-07-11 | 1987-01-22 | Dainippon Printing Co Ltd | Material feeling expressing method in expressing three-dimensional graphic form with two-dimension |
-
1987
- 1987-09-28 JP JP62240722A patent/JPH06102014B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6486867A (en) | 1989-03-31 |
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