JP2006288311A - Monitoring system for cultivation vessel - Google Patents

Monitoring system for cultivation vessel Download PDF

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Publication number
JP2006288311A
JP2006288311A JP2005115294A JP2005115294A JP2006288311A JP 2006288311 A JP2006288311 A JP 2006288311A JP 2005115294 A JP2005115294 A JP 2005115294A JP 2005115294 A JP2005115294 A JP 2005115294A JP 2006288311 A JP2006288311 A JP 2006288311A
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culture
vessel
container
monitoring system
sealing
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JP2005115294A
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Japanese (ja)
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Hiroshi Tachikui
宏 立久井
Tsutomu Suzuki
力 鈴木
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Hitachi Healthcare Manufacturing Ltd
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Hitachi Medical Corp
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Priority to JP2005115294A priority Critical patent/JP2006288311A/en
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    • 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/40Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure

Abstract

<P>PROBLEM TO BE SOLVED: To provide a monitoring system for cultivation vessel that can confirm the shut tightness of the culture system. <P>SOLUTION: This culture vessel-monitoring system is equipped with a means for measuring the shut tightness of the whole culture vessel system comprising the reagent vessel, the cultivation vessel and the waste fluid vessel at discontinuous different time and the measurement of shut tightness of the whole vessel system is carried out at least once. The measurement is carried out by measuring the amount of the air injected into the vessels and these operations are backed up with a pressure sensor set at the culture apparatus and with the gas charging. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

本発明は、本発明は試薬容器・培養ユニット・廃液容器が一体となり、かつそれらの制御をバルブ制御及び培養ユニットの可動制御により細胞を培養する装置に関する。   The present invention relates to an apparatus for culturing cells by integrating a reagent container, a culture unit, and a waste liquid container, and controlling them by valve control and movable control of the culture unit.

細胞培養を機械により自動的に行うメリットとして、煩雑な培養操作を自動化する以外に、コンタミネーション等の汚染を防止するというものがある。この場合、細胞に液体・気体等を介して外部と直接触れる部分を極力少なくすることが望ましい。そこで、試薬容器・培養ユニット・廃液容器が一体となり閉鎖構造をとり、かつそれらの制御をバルブ制御及び培養ユニットの可動制御により細胞を培養する培養システムを用いるとその条件を十分に満たすことになる。その上で、一体となった培養システムが閉鎖的な構造保持したまま培養できたことを証明することが好ましい。これは、培養するサンプルに対してコンタミネーション等の外部汚染が生じていないことを(トレーサビリティの確保等のため)担保させるために必要である。(例えば特許文献1)
特開平6-261736号公報
Advantages of automatically performing cell culture by a machine include prevention of contamination such as contamination in addition to automating complicated culture operations. In this case, it is desirable to minimize as much as possible the portion that directly touches the outside via a liquid or gas. Therefore, a reagent container, a culture unit, and a waste liquid container are integrated to form a closed structure, and these conditions are sufficiently satisfied by using a culture system for culturing cells by valve control and movable control of the culture unit. . In addition, it is preferable to prove that the integrated culture system can be cultured while maintaining the closed structure. This is necessary to ensure that the sample to be cultured is free from external contamination such as contamination (for ensuring traceability). (For example, Patent Document 1)
Japanese Unexamined Patent Publication No. 6-2161736

事前に品質管理等で密閉性を確認できた容器を培養に用いることはできるが、実際に培養することによって容器システムの閉鎖性に変化が生じずに培養を行ったか否かを調べる方法が存在しない。特に、チューブ・バック等の組み合わせた培養システムの場合、部品点数の多さや構造上の複雑さからくる、個々の容器及び各容器構成間におけるばらつき、劣化、破損の可能性が高く、かつその検出は困難である。本発明の目的は、培養システムの閉鎖性の確認を行うことである。   Containers that have been confirmed to be sealed by quality control in advance can be used for culturing, but there is a method to check whether culturing has been performed without any change in the closure of the container system by actual culturing. do not do. In particular, in the case of a culture system that combines tubes and bags, there is a high possibility of variation, deterioration, and breakage between individual containers and each container configuration due to the large number of parts and structural complexity, and the detection thereof. It is difficult. The object of the present invention is to confirm the closure of the culture system.

本課題を解決させるため、試薬容器・培養容器・廃液容器が一体となって培養を行う装置における容器システム全体の密閉度の測定を、連続していない異なる時期に行う手段を備えた。容器システム全体の密閉度の測定を、少なくとも1回以上行う。また、計測を容器内へ注入された空気量を測定することにより行い、それらを培養装置システムに設けた圧力センサとガス充填により支援する。   In order to solve this problem, there is provided means for measuring the sealing degree of the entire container system in a device that cultures in an integrated manner with a reagent container, a culture container, and a waste liquid container at different times. Make at least one measurement of the tightness of the entire container system. Moreover, measurement is performed by measuring the amount of air injected into the container, and these are supported by a pressure sensor provided in the culture apparatus system and gas filling.

本発明によれば、培養システムの閉鎖性の確認を行うことができる。   According to the present invention, it is possible to confirm the closing property of the culture system.

本発明は試薬容器・培養ユニット・廃液容器が一体となり、かつそれらの制御をバルブ及び培養ユニットの可動等による制御により細胞を培養する装置において、培養容器システムの取り付けから、培養中及び培養終了後の取り外しまでの間で密閉度を測定する。その上で、さらに異なる時期に密閉度を測定するか、あらかじめ記録された密閉度を入手する。そして、それらの変化量を測定することにより容器システムの閉鎖性が維持できたとことを証明する。   The present invention is an apparatus in which a reagent container, a culture unit, and a waste liquid container are integrated and the cells are cultured by controlling the valve and the culture unit by moving the culture unit. Measure the sealing degree until the removal of. In addition, the sealing degree is measured at a different time or a pre-recorded sealing degree is obtained. And it proves that the closure nature of the container system was able to be maintained by measuring those changes.

培養装置システムに培養システムを設置した直後と、培養終了後に密閉度を測定して、閉鎖的な環境で培養されたことを担保した例である。   This is an example in which the degree of sealing was measured immediately after the culture system was installed in the culture apparatus system and after the culture was completed to ensure that the culture was performed in a closed environment.

本実施例では、図1に示す形態の細胞培養装置システムを用いる。具体的には、図1の構成要素4,2,10の各部分が一体となった部分(細胞培養ユニット)及びそれ以外の部分(培養システム本体)で細胞培養を行う。細胞培養ユニット中の試薬容器4は保存庫3で低温に維持され、培養ユニット2は培養槽1により細胞培養に適した条件(一般的な動物細胞の場合37oC・5%CO2)下に設定している。試薬容器4から培養ユニット2への溶液の注入及び培養ユニット2から廃液ボトル10への廃液の移動は、それぞ試薬制御弁41及び供給側ポンプ8、廃液制御弁42及び廃液側ポンプ9により制御されており、かつその動作自体は制御装置32によりコントロールされている。これらの構成により培養ユニット2内にある細胞は、培地交換や培養環境の維持等において直接手作業を介さずに行うことが出来る。   In this embodiment, a cell culture apparatus system having the configuration shown in FIG. 1 is used. Specifically, cell culture is performed in a part (cell culture unit) in which the parts 4, 2, and 10 in FIG. 1 are integrated, and the other part (culture system main body). The reagent container 4 in the cell culture unit is kept at a low temperature in the storage chamber 3, and the culture unit 2 is set in the culture tank 1 under conditions suitable for cell culture (37oC / 5% CO2 for general animal cells). ing. The injection of the solution from the reagent container 4 to the culture unit 2 and the movement of the waste liquid from the culture unit 2 to the waste liquid bottle 10 are controlled by the reagent control valve 41 and the supply side pump 8, the waste liquid control valve 42 and the waste liquid side pump 9, respectively. The operation itself is controlled by the control device 32. With these configurations, the cells in the culture unit 2 can be carried out without direct manual work in exchanging the medium or maintaining the culture environment.

実際に培養を行う際に、作業者は試薬容器4、培養ユニット2及び廃液ボトル10が一体となって形成された細胞培養ユニットを培養システム本体に取り付ける。その後、排気制御弁43を閉めたうえで吸入ポンプ33から吸気側フィルタ11を経由することによりクリーンな空気を送り込む。送り込んだ空気の圧力は吸気側圧力センサ13及び排気側圧力センサ21にて測定する。2つの圧力の違いにより、細胞培養ユニット内の密閉度を測定する。また、排気側フィルタ22に設けたフィルタにより万が一、空気等が逆流しても培養システム内部が汚染しないようになっている。本培養システムを用いて細胞を培養した後に、再度排気制御弁43を閉めたうえで吸入ポンプ33から吸気側フィルタ11を経由することによりクリーンな空気を送り込む。送り込んだ空気の圧力は吸気側圧力センサ13及び排気側21にて測定する。2つの圧力の違いにより、細胞培養ユニット内の密閉度を測定する。これらの制御及び測定は、手動もしくは制御装置32により自動的に制御される。上記、二回の細胞培養システムの密閉度の変化を記録することで、細胞培養システム内の、細胞培養等による破損・劣化を検出することが出来る。逆に、問題が生じない場合は、培養期間の間容器の破損・劣化が生じずに培養することが出来たと証明することができる。   When the culture is actually performed, the operator attaches the cell culture unit in which the reagent container 4, the culture unit 2 and the waste liquid bottle 10 are integrally formed to the culture system main body. Thereafter, after the exhaust control valve 43 is closed, clean air is sent from the suction pump 33 through the intake side filter 11. The pressure of the supplied air is measured by the intake side pressure sensor 13 and the exhaust side pressure sensor 21. The degree of sealing in the cell culture unit is measured by the difference between the two pressures. In addition, the filter provided in the exhaust side filter 22 prevents the inside of the culture system from being contaminated even if air or the like flows backward. After culturing cells using the main culture system, the exhaust control valve 43 is closed again, and clean air is sent from the suction pump 33 through the intake side filter 11. The pressure of the supplied air is measured by the intake side pressure sensor 13 and the exhaust side 21. The degree of sealing in the cell culture unit is measured by the difference between the two pressures. These controls and measurements are controlled manually or automatically by the control device 32. By recording the change in the sealing degree of the cell culture system twice as described above, it is possible to detect damage or deterioration due to cell culture or the like in the cell culture system. On the contrary, if no problem occurs, it can be proved that the culture was possible without damaging or deteriorating the container during the culture period.

養終了後に密閉度を測定して、あらかじめ規定された密閉度と比較して閉鎖的な環境で培養されたことを担保した例。   An example in which the degree of sealing was measured after the completion of cultivation, and the culture was ensured in a closed environment as compared with a predetermined degree of sealing.

本実施例では、図2に示す形態の細胞培養装置システムを用いる。本システムは、培養システム本体と、図2に示される細胞培養ユニットに分別される。培養システム本体の基本的な構成は実施例1に準じるが、相違点として記録デバイス51と、その情報を読み取り制御装置32に伝える情報読み取り装置がある。そのため、取り付ける際にあらかじめ記録されていた培養システム本体の密閉度を読み取ることができる。   In this embodiment, a cell culture apparatus system having the configuration shown in FIG. 2 is used. This system is divided into a culture system main body and a cell culture unit shown in FIG. The basic configuration of the culture system main body is the same as that of the first embodiment, but there is a recording device 51 and an information reading device that transmits the information to the reading control device 32 as a difference. Therefore, the sealing degree of the culture system main body recorded in advance at the time of attachment can be read.

本構成を採用することにより、作業者は試薬容器4、培養ユニット2及び廃液ボトル10が一体となって形成された細胞培養ユニットを培養システム本体に取り付け、細胞を培養した後に、排気制御弁43を閉めたうえで吸入ポンプ33から吸気側フィルタ11を経由することによりクリーンな空気を送り込む。送り込んだ空気の圧力は吸気側圧力センサ13及び排気側圧力センサ21にて密閉度を測定する。本圧力と事前に装置に設定されていた2つの密閉度の違いにより、細胞培養ユニット内培養中における密閉度を推定する。これらの制御及び測定は、手動もしくは制御装置32により自動的に制御される。   By adopting this configuration, the operator attaches the cell culture unit formed integrally with the reagent container 4, the culture unit 2 and the waste liquid bottle 10 to the culture system body, and after culturing the cells, the exhaust control valve 43 Then, clean air is sent from the suction pump 33 via the intake side filter 11. The pressure of the supplied air is measured by an intake side pressure sensor 13 and an exhaust side pressure sensor 21 for sealing. The degree of sealing during the cultivation in the cell culture unit is estimated from the difference between this pressure and the two sealing degrees set in the device in advance. These controls and measurements are controlled manually or automatically by the control device 32.

上記、培養容器の密閉度を培養終了後に測定して、あらかじめ個々の容器に設定された密閉度の比較を行うことで、細胞培養システム内の細胞培養等による破損・劣化を検出することが出来る。逆に、問題が生じない場合は、培養期間の間容器の破損・劣化が生じずに培養することができる。   By measuring the degree of sealing of the culture container after completion of the culture and comparing the degree of sealing previously set for each container, it is possible to detect damage or deterioration due to cell culture or the like in the cell culture system. . On the other hand, if no problem occurs, the culture can be performed without causing breakage or deterioration of the container during the culture period.

本発明の実施例1を示す図。1 is a diagram showing Example 1 of the present invention. FIG. 本発明の実施例2を示す図。FIG. 4 is a diagram showing Example 2 of the present invention.

符号の説明Explanation of symbols

1 培養槽、2 培養ユニット、3 保存庫、4 試薬容器、6 注入流路、8 供給側ポンプ、9 廃液側ポンプ、10 廃液ポンプ、11 吸気側フィルタ、13 吸気側圧力センサ、21 排気側圧力センサ、22 排気側フィルタ、32 制御装置、33 吸入ポンプ、41 試薬制御弁、42 廃液制御弁、43 排気制御弁   DESCRIPTION OF SYMBOLS 1 Culture tank, 2 Culture unit, 3 Storage box, 4 Reagent container, 6 Injection flow path, 8 Supply side pump, 9 Waste liquid side pump, 10 Waste liquid pump, 11 Intake side filter, 13 Intake side pressure sensor, 21 Exhaust side pressure Sensor, 22 Exhaust side filter, 32 Control device, 33 Suction pump, 41 Reagent control valve, 42 Waste liquid control valve, 43 Exhaust control valve

Claims (3)

試薬容器・培養容器・廃液容器が一体となって培養を行う装置における容器システム全体の密閉度の測定を、連続していない異なる時期に行う手段を備えた培養容器モニタリングシステム。   A culture container monitoring system comprising means for measuring the degree of sealing of the entire container system in a device that cultures a reagent container, a culture container, and a waste liquid container in an integrated manner at different times that are not continuous. 容器システム全体の密閉度の測定を、少なくとも1回以上行うことを特徴とする請求項1記載の培養容器モニタリングシステム。   The culture vessel monitoring system according to claim 1, wherein the measurement of the sealing degree of the whole vessel system is performed at least once. 計測を容器内へ注入された空気量を測定することにより行い、それらを培養装置システムに設けた圧力センサとガス充填により支援する請求項1乃至2のいずれかに記載の培養容器モニタリングシステム。   The culture vessel monitoring system according to any one of claims 1 to 2, wherein the measurement is performed by measuring the amount of air injected into the vessel and is supported by a pressure sensor provided in the culture device system and gas filling.
JP2005115294A 2005-04-13 2005-04-13 Monitoring system for cultivation vessel Pending JP2006288311A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001504692A (en) * 1996-11-01 2001-04-10 ジーンスパン コーポレイション Cell culture incubator

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001504692A (en) * 1996-11-01 2001-04-10 ジーンスパン コーポレイション Cell culture incubator

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