JPH078260A - Continuous culture unit - Google Patents
Continuous culture unitInfo
- Publication number
- JPH078260A JPH078260A JP15037493A JP15037493A JPH078260A JP H078260 A JPH078260 A JP H078260A JP 15037493 A JP15037493 A JP 15037493A JP 15037493 A JP15037493 A JP 15037493A JP H078260 A JPH078260 A JP H078260A
- Authority
- JP
- Japan
- Prior art keywords
- culture
- medium
- valve
- gas
- tank
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/26—Constructional details, e.g. recesses, hinges flexible
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/18—External loop; Means for reintroduction of fermented biomass or liquid percolate
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Clinical Laboratory Science (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は研究室または産業的に実
施される胞または微生物の液体中における連続培養に適
用される培養ユニットに関する。FIELD OF THE INVENTION The present invention relates to a culture unit adapted for continuous culture in a liquid of cells or microorganisms, which is carried out in a laboratory or industrially.
【０００２】[0002]
【従来の技術】従来の細胞を連続的かつ長期間培養する
装置はあったが、培地を循環させる配管をガス透過性チ
ューブで構成し、該配管内を流す培養液の循環量を増減
させることで培養液内の溶存酸素濃度、炭酸ガス濃度を
制御していた。その一方で、配管に接続された培養容器
で培養されている細胞に対する栄養素の供給も培養液の
循環量によっていた。そのため、従来の培養装置では、
配管からの気泡の混入の危険性が高く、培養状態の
状況にかゝわらず培養液量が変更してしまい定常的な培
養ができないという問題点があり、さらに新鮮培地と
廃液のタンクを個別にもっているのでユニットの小型を
妨げるという問題点もあった。2. Description of the Related Art Although there has been a conventional apparatus for continuously culturing cells for a long period of time, a pipe for circulating a culture medium is composed of a gas permeable tube to increase or decrease the circulation amount of a culture solution flowing through the pipe. The dissolved oxygen concentration and carbon dioxide concentration in the culture solution were controlled by. On the other hand, the supply of nutrients to the cells cultured in the culture vessel connected to the pipe was also dependent on the circulation amount of the culture solution. Therefore, in the conventional culture device,
There is a high risk of air bubbles entering from the piping, and there is a problem that the amount of culture solution will change regardless of the culture condition and constant culture cannot be performed.Furthermore, separate tanks for fresh medium and waste solution are required. Since it has it, there was also a problem that it hindered the miniaturization of the unit.
【０００３】[0003]
【発明が解決しようとする課題】本発明は上記技術水準
に鑑み、細胞、微生物の培養環境を一定に保持しながら
ガス交換をすることが可能であり、新鮮培地と廃液のタ
ンクを１つにすることによってユニットを小型化するこ
とができる培養ユニットを提供しようとするものであ
る。In view of the above-mentioned state of the art, the present invention enables gas exchange while maintaining a constant culture environment for cells and microorganisms, and has a single tank for fresh medium and waste liquid. By doing so, it is intended to provide a culture unit that can be miniaturized.
【０００４】[0004]
【課題を解決するための手段】本発明は細胞または微生
物の培養容器、該培養容器の培地を培地循環ポンプを介
して、センサ部及びＯ2 ，ＣＯ2 ，Ｎ2 ガスを供給する
第１バルブを備えたガス透過性チューブを内蔵したガス
交換部を経由させて該培養容器に返送する配管、柔軟性
素材よりなる新鮮培地タンクと柔軟性素材よりなる廃液
タンクとを内蔵した固い収納容器、該新鮮培地タンクの
新鮮培地を新鮮培地供給ポンプを介して、第２バルブ、
前記培養容器、第３バルブを経由させて前記廃液タンク
に供給する配管及び前記センサ部からの信号を受け前記
各ポンプ並びにバルブを制御する制御部を具備してなる
ことを特徴とする連続培養ユニットである。The present invention relates to a cell or microorganism culture vessel, and a first valve for supplying a sensor portion and O 2 , CO 2 , N 2 gas to a medium in the culture vessel via a medium circulation pump. A pipe for returning to the culture container via a gas exchange section containing a gas permeable tube having a hard storage container containing a fresh medium tank made of a flexible material and a waste liquid tank made of a flexible material, The fresh medium in the fresh medium tank is passed through the fresh medium supply pump to the second valve,
A continuous culture unit comprising: the culture vessel, a pipe for supplying the waste liquid tank via a third valve, and a control unit for receiving signals from the sensor unit and controlling the pumps and valves. Is.
【０００５】[0005]
【作用】細胞または微生物を培養するための培養容器に
ガスの透過性のないチューブまたは配管を用いてバル
ブ，ポンプ，培地の性状をモニタするセンサ部，ガス交
換部を取り付ける。ガス交換部はガス透過性のある素材
でできたチューブを取り付け培地に接触するようにす
る。ガス透過性チューブには加圧された酸素ガス，ＣＯ
2 ガス，窒素ガスをバルブ操作によって流れるようにす
る。これにより下記作用が可能となる。[Function] A valve, a pump, a sensor unit for monitoring the property of the medium, and a gas exchange unit are attached to a culture container for culturing cells or microorganisms by using a tube or pipe impermeable to gas. The gas exchange part is equipped with a tube made of a gas permeable material so as to come into contact with the culture medium. Pressurized oxygen gas, CO
2 Allow the gas and nitrogen gas to flow by operating the valve. This enables the following actions.
【０００６】（１）培養液を循環することにより、細胞
に対して、生育に必要な栄養素を充分に与えることが可
能となり、細胞または微生物の排出する代謝物により生
育環境が適さない状態となるまで培地を消費することな
く長期の培養が可能となる。(1) By circulating the culture broth, it becomes possible to sufficiently supply the cells with nutrients necessary for growth, and metabolites excreted by the cells or microorganisms make the growth environment unsuitable. It enables long-term culture without consuming the medium.
【０００７】（２）培地の循環ラインにガス交換部を取
り付け、ガス透過性チューブに流すガスの量を制御する
ことによって、培地の循環量を変化させることなくガス
交換を実施でき、細胞の生育状況を変化させることがな
いため、培養状態を一定に保つことが可能となる。(2) By attaching a gas exchange part to the circulation line of the medium and controlling the amount of gas flowing through the gas permeable tube, gas exchange can be carried out without changing the circulation amount of the medium, and cell growth Since the situation is not changed, the culture state can be kept constant.
【０００８】（３）また配管をガス透過性のない素材に
することによって配管，バルブ等に気泡の発生を抑える
ことが可能となり培地循環不良を防止することが可能と
なる。(3) Further, when the pipe is made of a material having no gas permeability, it is possible to suppress the generation of bubbles in the pipe, the valve and the like, and it is possible to prevent the poor circulation of the medium.
【０００９】また上記ユニットの循環ラインに取りつけ
たセンサ部によって培地の性状をモニタし、本発明の培
養ユニットに組込んだ制御装置により培地循環量の判
断、ガス透過性チューブへ流すガス量の判断、培地交換
の判断、植え継ぎの判断を行う。この判断により、ポン
プ、培地中のガス交換及び培地交換ラインに組込んだ培
地タンク及び廃液タンクのバルブを制御することによ
り、培地循環量の変更、ガス交換量の一定化、培地の交
換、細胞または微生物の植え継ぎを自動的に実施するこ
とが可能となる。Further, the property of the culture medium is monitored by a sensor unit attached to the circulation line of the above unit, and the control unit incorporated in the culture unit of the present invention determines the circulation amount of the culture medium and the amount of gas flowing to the gas permeable tube. , Determine the medium replacement, and determine the transplanting. Based on this judgment, by controlling the pump, the gas exchange in the medium and the valves of the medium tank and the waste liquid tank installed in the medium exchange line, the medium circulation amount can be changed, the gas exchange amount can be kept constant, the medium can be exchanged, and the cells can be replaced. Alternatively, it becomes possible to automatically carry out the subculture of microorganisms.
【００１０】また、培地タンクと廃液タンクを同一容器
内に柔軟性の材質で作られた袋にすることによって、２
つの独立した容器から１つの容器にすることが可能とな
りユニットの小型化を可能とする。[0010] In addition, by using a bag made of a flexible material in the same container as the medium tank and the waste liquid tank,
It is possible to reduce the unit size from one independent container to one.
【００１１】[0011]
【実施例】以下、本発明の一実施例を図１〜図４によっ
て説明する。図１〜図４において、１は細胞培養容器で
あり、その配管６には培地循環ポンプ２、ガス交換部
３、センサ部５が取り付けられている。ガス交換部３内
部にはガス交換チューブ４が組み込まれ、第１バルブ７
が接続され、酸素，二酸化炭素，窒素ガスを通すように
されている。培地タンク１０及び廃液タンク１１は柔軟
性の素材で作られたバックであり、１つの固い収納容器
１４に内蔵されている。収納容器１４は配管６′によっ
て新鮮培地供給ポンプ９、第２バルブ８、第３バルブ１
２が接続され、培養容器１に接続される。また、制御部
１３はセンサ部５からの信号を受けて各ポンプ、バルブ
の制御を行うように構成されている。なお、図１中、実
線は流体の流れ、点線は制御信号の流れを示す。DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of the present invention will be described below with reference to FIGS. 1 to 4, reference numeral 1 is a cell culture container, and a pipe 6 is provided with a culture medium circulation pump 2, a gas exchange unit 3, and a sensor unit 5. The gas exchange tube 4 is installed inside the gas exchange section 3, and the first valve 7
Are connected to pass oxygen, carbon dioxide, and nitrogen gas. The culture medium tank 10 and the waste liquid tank 11 are bags made of a flexible material and are contained in one solid storage container 14. The storage container 14 is provided with a fresh medium supply pump 9, a second valve 8 and a third valve 1 through a pipe 6 '.
2 is connected to the culture container 1. Further, the control unit 13 is configured to receive signals from the sensor unit 5 and control each pump and valve. In addition, in FIG. 1, the solid line indicates the flow of fluid, and the dotted line indicates the flow of control signals.
【００１２】定常状態においては、図２に示すように、
センサ部５の信号を制御部１３が受け、培地循環ポンプ
２を制御することによって培地を循環させ培養容器１内
に栄養素を供給する。なお、図２中、太い実線は流体の
流れ、太い点線は制御信号の流れを示す。In the steady state, as shown in FIG.
The control unit 13 receives a signal from the sensor unit 5 and controls the medium circulation pump 2 to circulate the medium and supply nutrients into the culture container 1. In FIG. 2, a thick solid line shows a fluid flow and a thick dotted line shows a control signal flow.
【００１３】次に、培地内のガス交換においては図３に
示すように、培地を循環させる制御とは独立して、セン
サ部５の信号を受け制御部１３によってガス透過性チュ
ーブ４に取り付けた第１バルブ７を制御することによ
り、ガス透過性チューブ４内に酸素，窒素，二酸化炭素
ガスを通気させ培地内のガス交換を実施する。このこと
により、培地循環量の制御とガス交換の制御を別々にも
つことが可能となり、細胞または微生物の生育環境を一
定に保つことができる。図３において、太い実線、太い
点線は図２と同じ意味をもつ。Next, in the gas exchange in the medium, as shown in FIG. 3, the signal from the sensor section 5 is received and the control section 13 attaches it to the gas permeable tube 4 independently of the control of circulating the medium. By controlling the first valve 7, oxygen, nitrogen, and carbon dioxide gas are passed through the gas permeable tube 4 to exchange gas in the medium. This makes it possible to separately control the amount of medium circulation and the control of gas exchange, and it is possible to keep the growth environment of cells or microorganisms constant. In FIG. 3, thick solid lines and thick dotted lines have the same meaning as in FIG.
【００１４】培地交換及び植え継ぎにおいては図４に示
すように、センサ部５からの信号によって、制御部１３
から、第３バルブ８、新鮮培地供給ポンプ９、第３バル
ブ１２を制御し、培地交換及び植え継ぎを行う。ここで
収納容器１４に内蔵した培地タンク１０及び廃液タンク
１１は培地タンク１０より新鮮培地を新鮮培地供給ポン
プ９を用いて取り出す。このとき培地タンク１０は柔軟
性の材質でできているため縮むことになる。また培養容
器１に供給された分と同量の廃液が廃液タンク１１に流
入する。廃液タンク１１もまた柔軟性の材質でできてい
るため廃液の流入によってふくらむことになる。このこ
とにより培地、廃液タンク１０、１１を一体化すること
が可能となりユニットの小型化を可能とする。図４にお
いて、太い実線、太い点線は図２と同じ意味をもつ。In the medium replacement and the transfer, as shown in FIG. 4, the control unit 13 is operated by the signal from the sensor unit 5.
From the above, the third valve 8, the fresh medium supply pump 9, and the third valve 12 are controlled to perform medium exchange and subculture. Here, the medium tank 10 and the waste liquid tank 11 built in the storage container 14 take out the fresh medium from the medium tank 10 by using the fresh medium supply pump 9. At this time, since the culture medium tank 10 is made of a flexible material, it will shrink. Further, the same amount of waste liquid as that supplied to the culture container 1 flows into the waste liquid tank 11. Since the waste liquid tank 11 is also made of a flexible material, it swells when the waste liquid flows in. As a result, the medium and the waste liquid tanks 10 and 11 can be integrated, and the unit can be downsized. In FIG. 4, thick solid lines and thick dotted lines have the same meaning as in FIG.
【００１５】以上詳述したように、この実施例は、培養
容器にバルブ、培地循環ポンプセンサ部及びガス交換部
を取り付け、また、培地交換、植え継ぎのための廃液タ
ンク、培地タンク、新鮮培地供給ポンプ、バルブを取り
付け、制御部を組み込むことにより細胞または微生物の
長期無人自動培養を可能とし、ガス交換部を独立しても
つことにより培地循環量を変化させることなくガス交換
を行うことが可能となる。このことにより細胞または微
生物の生育環境を一定に保ちがなら培養が可能となる。
また廃液タンク及び培地タンクを柔軟性の材質で制作す
ることによって２つのタンクを１つの容器に一体化する
ことが可能となり、ユニットの小型化が可能となる。As described in detail above, in this embodiment, a valve, a medium circulation pump sensor section and a gas exchange section are attached to a culture vessel, and a waste liquid tank for medium exchange and transfer, a medium tank, and a fresh medium. By installing a supply pump and valve and incorporating a control unit, long-term unattended automatic culture of cells or microorganisms is possible, and by having an independent gas exchange unit, it is possible to perform gas exchange without changing the medium circulation amount. Becomes This enables culturing if the growth environment of cells or microorganisms can be kept constant.
Further, by manufacturing the waste liquid tank and the culture medium tank with flexible materials, the two tanks can be integrated into one container, and the unit can be downsized.
【００１６】[0016]
【発明の効果】本発明の培養ユニットによれば、細胞ま
たは微生物の長期無人自動培養が可能となり、しかも培
地循環量を変化させることなくガス交換を行うことが可
能となる。このことによって配管中への気泡の浸入の防
止及び培養環境を一定に保持しながら培養が可能とな
る。また培地タンク及び廃液タンクを一体化することが
可能となりユニットの小型化が可能となる効果を奏す
る。EFFECTS OF THE INVENTION The culture unit of the present invention enables long-term unattended automatic culture of cells or microorganisms, and also allows gas exchange without changing the circulating amount of the medium. As a result, it becomes possible to prevent bubbles from entering the pipe and perform culture while keeping the culture environment constant. In addition, the culture medium tank and the waste liquid tank can be integrated, and the unit can be downsized.
【図１】本発明の実施例に係る系統図。FIG. 1 is a system diagram according to an embodiment of the present invention.
【図２】図１の定常時における流体及び制御信号の流れ
を示す説明図。FIG. 2 is an explanatory diagram showing a flow of a fluid and a control signal in a steady state of FIG.
【図３】図１のガス交換時における流体及び制御信号の
流れを示す説明図。FIG. 3 is an explanatory diagram showing the flow of fluid and control signals during the gas exchange of FIG.
【図４】図１の培地交換、植え継ぎ時の流体及び制御信
号の流れを示す説明図。FIG. 4 is an explanatory diagram showing the flow of fluid and control signals at the time of medium replacement and transplantation of FIG. 1.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 村上 敬司 東京都港区浜松町２丁目４番１号 宇宙開 発事業団内 (72)発明者 根岸 成昭 兵庫県神戸市兵庫区和田崎町一丁目１番１ 号 三菱重工業株式会社神戸造船所内 (72)発明者 落合 俊昌 兵庫県神戸市兵庫区和田崎町一丁目１番１ 号 三菱重工業株式会社神戸造船所内 ─────────────────────────────────────────────────── ─── Continued Front Page (72) Inventor Keiji Murakami 2-4-1, Hamamatsucho, Minato-ku, Tokyo Inside Space Development Enterprise (72) Inventor Naruaki Negishi 1-chome Wadazakicho, Hyogo-ku, Kobe-shi, Hyogo No. 1-1 Mitsubishi Heavy Industries, Ltd. Kobe Shipyard (72) Inventor Toshinsho Ochiai 1-1-1 Wadazakicho, Hyogo-ku, Hyogo Prefecture Kobe City Mitsubishi Heavy Industries, Ltd. Kobe Shipyard
Claims (1)
器の培地を培地循環ポンプを介して、センサ部及び
Ｏ2 ，ＣＯ2 ，Ｎ2 ガスを供給する第１バルブを備えた
ガス透過性チューブを内蔵したガス交換部を経由させて
該培養容器に返送する配管、柔軟性素材よりなる新鮮培
地タンクと柔軟性素材よりなる廃液タンクとを内蔵した
固い収納容器、該新鮮培地タンクの新鮮培地を新鮮培地
供給ポンプを介して、第２バルブ、前記培養容器、第３
バルブを経由させて前記廃液タンクに供給する配管及び
前記センサ部からの信号を受け前記各ポンプ並びにバル
ブを制御する制御部を具備してなることを特徴とする連
続培養ユニット。1. A cell or microorganism culture container, a gas permeable tube having a sensor part and a first valve for supplying O 2 , CO 2 and N 2 gas to a medium in the culture container via a medium circulation pump. A pipe for returning to the culture container via a gas exchange section containing a built-in, a hard storage container containing a fresh medium tank made of a flexible material and a waste liquid tank made of a flexible material, and a fresh medium in the fresh medium tank. The second valve, the culture vessel, the third valve via the fresh medium supply pump.
A continuous culture unit comprising a pipe for supplying the waste liquid tank via a valve and a control unit for receiving signals from the sensor unit and controlling the pumps and valves.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15037493A JP3453167B2 (en) | 1993-06-22 | 1993-06-22 | Continuous culture unit |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15037493A JP3453167B2 (en) | 1993-06-22 | 1993-06-22 | Continuous culture unit |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH078260A true JPH078260A (en) | 1995-01-13 |
| JP3453167B2 JP3453167B2 (en) | 2003-10-06 |
Family
ID=15495600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15037493A Expired - Fee Related JP3453167B2 (en) | 1993-06-22 | 1993-06-22 | Continuous culture unit |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3453167B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003048296A1 (en) * | 2001-12-05 | 2003-06-12 | Takagi Industrial Co., Ltd. | Cell/tissue culture apparatus |
| JP2017143775A (en) * | 2016-02-17 | 2017-08-24 | 東洋紡株式会社 | Cell culture apparatus using gas-impermeable tube and cell culture method |
| KR20190128546A (en) * | 2016-03-14 | 2019-11-18 | 라빈드라쿠마 디루바이 파텔 | Bioreactor System and Method |
-
1993
- 1993-06-22 JP JP15037493A patent/JP3453167B2/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003048296A1 (en) * | 2001-12-05 | 2003-06-12 | Takagi Industrial Co., Ltd. | Cell/tissue culture apparatus |
| US7541178B2 (en) | 2001-12-05 | 2009-06-02 | Takagi Industrial Co., Ltd. | Cell/tissue culture apparatus |
| JP2017143775A (en) * | 2016-02-17 | 2017-08-24 | 東洋紡株式会社 | Cell culture apparatus using gas-impermeable tube and cell culture method |
| KR20190128546A (en) * | 2016-03-14 | 2019-11-18 | 라빈드라쿠마 디루바이 파텔 | Bioreactor System and Method |
| US11365382B2 (en) | 2016-03-14 | 2022-06-21 | Omnibrx Biotechnologies Private Limited | Bioreactor system and method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3453167B2 (en) | 2003-10-06 |
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