JP2001231544A - Method for controlling operation of aerated spinner culture tank - Google Patents

Method for controlling operation of aerated spinner culture tank

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Publication number
JP2001231544A
JP2001231544A JP2000052312A JP2000052312A JP2001231544A JP 2001231544 A JP2001231544 A JP 2001231544A JP 2000052312 A JP2000052312 A JP 2000052312A JP 2000052312 A JP2000052312 A JP 2000052312A JP 2001231544 A JP2001231544 A JP 2001231544A
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JP
Japan
Prior art keywords
gas
distribution
tank
dissolved oxygen
oxygen concentration
Prior art date
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Granted
Application number
JP2000052312A
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Japanese (ja)
Other versions
JP4103288B2 (en
Inventor
Toru Kasugai
徹 春日井
Sei Murakami
聖 村上
Susumu Harada
原田  進
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Hitachi Ltd
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Hitachi Ltd
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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
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
    • 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

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  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

PROBLEM TO BE SOLVED: To provide a method for evaluating the operation of an aerated spin ner culture tank, comprising calculating the distribution of dissolved air concentrations and controlling the concentrations so as to give the optimal distribution, while an aerated spinner culture tank has practically be manufac tured and then evaluated, because there has not been a method for evaluating and examining the operation conditions of the tank under the consideration of the concentration distribution of a solute gas, and further while the distribu tion of all the concentrations of dissolved oxygen could not be evaluated, although the concentration of the dissolved oxygen could be measured and then evaluated only at the measured point. SOLUTION: This method for controlling the operation of the aerated spinner culture tank, is characterized by calculating the distribution of gas movement volume coefficients kla, calculating the distribution of solute gas concentrations in the liquid from the calculation results, and then controlling the spinner revolution number, the gas flow volume, and the partial pressure or inner pressure of oxygen in the aerated gas in the culture tank so that the concentrations of the solute gas satisfy the culture conditions in all the areas in the tank.

Description

【発明の詳細な説明】DETAILED DESCRIPTION OF THE INVENTION

【0001】[0001]

【発明の属する技術分野】本発明は溶質ガスを液中に溶
解させまたは液中で発生したガスを液の外に追い出す必
要のある通気攪拌槽の運転制御方法に関する。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for controlling the operation of a ventilation stir tank in which a solute gas needs to be dissolved in a liquid or a gas generated in the liquid needs to be expelled out of the liquid.

【0002】[0002]

【従来の技術】攪拌槽内での化学反応や培養槽内での細
胞の呼吸などにより、酸素の消費や二酸化炭素の生成が
起きる槽では、最適な条件で化学反応や培養を行うため
に、槽内の全ての領域で酸素濃度または二酸化炭素濃度
が最適な範囲に収まるように、消費した酸素の補給もし
くは生成した二酸化炭素の除去が必要である。
2. Description of the Related Art In a tank in which oxygen is consumed or carbon dioxide is generated due to a chemical reaction in a stirring tank or respiration of cells in a culture tank, a chemical reaction or culture is performed under optimal conditions. It is necessary to replenish the consumed oxygen or remove the generated carbon dioxide so that the oxygen concentration or the carbon dioxide concentration is within the optimal range in all regions in the tank.

【0003】従来、通気撹拌槽内の溶存酸素や溶存二酸
化炭素の濃度分布を知るためにはCytotechnology,22,p8
7-94,1996,"Homogenisation and oxygen transfer rate
s inlarge agitated and sparged animal cell bioreac
tors:Some implications for growth and productio
n".Alvin W.Nienow etc. で論じられているように、実
際の通気撹拌槽を用いて濃度分布を予想するしかなく、
全く未知の通気撹拌槽内の濃度分布を定量的に予測する
ことは不可能であった。
[0003] Conventionally, in order to know the concentration distribution of dissolved oxygen and dissolved carbon dioxide in a ventilation stirring tank, Cytotechnology, 22, p8
7-94,1996, "Homogenisation and oxygen transfer rate
s inlarge agitated and sparged animal cell bioreac
tors: Some implications for growth and productio
n ". As discussed in Alvin W. Nienow etc., there is no choice but to predict the concentration distribution using an actual aeration stirred tank.
It was impossible to quantitatively predict the concentration distribution in a completely aerated stirred tank.

【0004】一方、攪拌槽内部の流れに関する数値解析
では、kla(ガス移動容量係数)の分布まで考慮に入れ
た物質濃度分布の計算はされていなかった。
On the other hand, in the numerical analysis of the flow inside the stirring tank, the calculation of the substance concentration distribution taking into account the distribution of kla (gas transfer capacity coefficient) was not performed.

【0005】また、溶存酸素濃度を制御する方法とし
て、特許第1552563号がある。これは溶存酸素濃度を測
定するセンサーを培養槽に設置して、その指示値に合わ
せて培養槽の運転条件を制御する方法である。
[0005] As a method for controlling the dissolved oxygen concentration, there is Japanese Patent No. 1556253. In this method, a sensor for measuring the concentration of dissolved oxygen is installed in a culture tank, and the operating conditions of the culture tank are controlled in accordance with the indicated value.

【0006】[0006]

【発明が解決しようとする課題】槽内の全ての領域にお
いて、溶質ガスの濃度を最適にすることを目的とした槽
の詳細構造及び運転条件の検討を行うには、槽の構造や
運転条件の変化が反映されるような方法で濃度を求める
必要がある。従来のような実際の槽を用いて濃度分布を
測定する方法では、構造を変化させた効果を知るために
は実際に槽を製作するしか方法はなかった。また、非接
触で定量的に濃度を測定することはできないので、槽内
分布の正確な測定は困難という問題もある。
In order to study the detailed structure and operating conditions of a tank for the purpose of optimizing the concentration of solute gas in all regions in the tank, the structure and operating conditions of the tank must be determined. It is necessary to determine the concentration by a method that reflects the change in the concentration. In the conventional method of measuring the concentration distribution using an actual tank, the only way to know the effect of changing the structure is to actually manufacture the tank. In addition, since the concentration cannot be quantitatively measured in a non-contact manner, there is also a problem that it is difficult to accurately measure the distribution in the tank.

【0007】また上記特許のような場合は、測定点にお
ける値しか評価できないため、槽内分布が適切かどうか
は判断できない、あるいは不明であった。すなわち攪拌
槽の溶質ガス濃度を制御するのに槽内の特定の点におけ
る測定値だけを直接用いる方法では、測定している点で
は濃度が最適であっても、他の点では溶質ガス濃度の過
不足が生じている可能性がある。したがって、溶質ガス
濃度を槽内の全ての領域で最適な範囲に収めるためには
槽内全体の溶質ガス濃度分布を何らかの方法で求める必
要がある。
Further, in the case of the above patent, it is impossible to judge whether the distribution in the tank is appropriate or unknown because only the value at the measurement point can be evaluated. That is, in the method of directly using only the measured value at a specific point in the tank to control the solute gas concentration in the stirring tank, even if the concentration is optimal at the point being measured, the solute gas concentration at other points is reduced. There may be excess or deficiency. Therefore, in order to keep the solute gas concentration within the optimum range in all regions in the tank, it is necessary to determine the solute gas concentration distribution in the entire tank by some method.

【0008】本発明の目的は、従来は定量的に予測する
ことが困難であった溶質ガス濃度の分布を計算評価し、
その評価結果によって運転条件を決定して制御する通気
攪拌槽の運転制御方法を提供することにある。
An object of the present invention is to calculate and evaluate the distribution of solute gas concentration, which was conventionally difficult to predict quantitatively,
It is an object of the present invention to provide a method for controlling the operation of a ventilation stirrer that determines and controls operating conditions based on the evaluation results.

【0009】[0009]

【課題を解決するための手段】本発明は、通気攪拌培養
槽内の溶質ガス濃度分布を最適に制御する方法であっ
て、前記槽内の複数点で溶存酸素濃度を計測し、前記槽
のガス移動容量係数の分布を求め、前記分布を用いて溶
存酸素濃度分布を演算し、前記計測された溶存酸素濃度
を用いて前記溶存酸素濃度分布を補正し、前記補正され
た溶存酸素濃度分布のうち培養条件から外れている領域
があるかどうかを判断し、培養条件から外れている領域
がある場合は溶存酸素濃度分布があらかじめ定められた
値になるまで前記培養槽の攪拌回転数、通気量、通気ガ
ス中の酸素分圧あるいは内圧を調整することを特徴とす
る。
SUMMARY OF THE INVENTION The present invention relates to a method for optimally controlling a solute gas concentration distribution in an aeration-stirred culture tank, wherein the dissolved oxygen concentration is measured at a plurality of points in the tank and the concentration of the dissolved oxygen is measured. Obtain the distribution of the gas transfer capacity coefficient, calculate the dissolved oxygen concentration distribution using the distribution, correct the dissolved oxygen concentration distribution using the measured dissolved oxygen concentration, and calculate the corrected dissolved oxygen concentration distribution. Judge whether there is a region out of the culture condition, and if there is a region out of the culture condition, the stirring rotation speed of the culture tank until the dissolved oxygen concentration distribution reaches a predetermined value, the amount of aeration. It is characterized in that the oxygen partial pressure or the internal pressure in the ventilation gas is adjusted.

【0010】前記槽のガス移動容量係数の分布は、槽内
の流れの乱流エネルギー散逸速度ε及びガスホールドア
ップαの分布をk-εモデル(乱流モデルの1つ)及びドリ
フトフラックスモデルあるいは2流体モデル(気液混相
流の効果を与える)の関数として有限差分法で計算す
る。酸素に対するklaの分布はを計算する。
[0010] The distribution of the gas transfer capacity coefficient of the tank is based on the k-ε model (one of the turbulence models) and the drift flux model. Calculated by the finite difference method as a function of a two-fluid model (giving the effect of gas-liquid multiphase flow). The distribution of kla for oxygen is calculated.

【0011】kla=kl・a kl=0.301So2 -1/2(εν)1/4 a=3α/Rb ただし、 kl:液境膜移動係数(m/s) So2:酸素のシュミット数 (=ν/Do2) ε:乱流エネルギー散逸速度(m2/s3) ν:動粘度(m2/s) Do2:液相中の酸素の拡散係数(m2/s) a:単位体積当たりの気液接触面積(1/m) α:ガスホールドアップ Rb:気泡半径(m) 上記で求めたklaの分布を用いて、次の式を有限差分法
により計算することで、溶存酸素濃度分布を求めること
ができる。
Kla = kl · a kl = 0.301 S o2 -1/2 (εν) 1/4 a = 3α / Rb where kl: liquid film transfer coefficient (m / s) S o2 : oxygen Schmitt number ( = ν / D o2 ) ε: Turbulent energy dissipation rate (m 2 / s 3 ) ν: Kinematic viscosity (m 2 / s) D o2 : Diffusion coefficient of oxygen in liquid phase (m 2 / s) a: Unit Gas-liquid contact area per volume (1 / m) α: Gas hold-up Rb: Bubble radius (m) Using the distribution of kla obtained above, calculate the following equation by the finite difference method to obtain dissolved oxygen The concentration distribution can be determined.

【0012】∂C/∂t = -div(C・(Ux,Uy,Uz))+DO22C+
kla(C*-C)+G ただし、 C :液中の溶存酸素濃度(mol/m3) (Ux,Uy,Uz) :流速ベクトル(m/s) kla :ガス移動容量係数(1/s) C* :飽和酸素濃度(mol/m3) (=p/H) p :水圧(atm) H :ヘンリー定数(atm・m3/mol) G :液中で単位体積・単位時間当たりに細胞が消費する
溶存酸素のモル数(mol/s・m) また、培養中の培養槽における複数の点での溶存酸素の
測定データを用いて上記の計算方法により溶存酸素濃度
分布の計算を行い、その結果を利用して培養槽の溶存酸
素濃度が槽内の全ての領域で培養条件を満たしているよ
うに運転制御をおこなう。
∂C / ∂t = -div (C · (Ux, Uy, Uz)) + D O22 C +
kla (C * -C) + G where C: dissolved oxygen concentration in liquid (mol / m 3 ) (Ux, Uy, Uz): flow velocity vector (m / s) kla: gas transfer capacity coefficient (1 / s ) C * : Saturated oxygen concentration (mol / m 3 ) (= p / H) p: Water pressure (atm) H: Henry's constant (atm ・ m 3 / mol) G: Cells per unit volume / time in liquid The number of moles of dissolved oxygen consumed by (mol / s · m 3 ) In addition, the dissolved oxygen concentration distribution is calculated by the above calculation method using the measured data of dissolved oxygen at a plurality of points in the culture tank during the culture. Using the results, operation control is performed such that the dissolved oxygen concentration in the culture tank satisfies the culture conditions in all regions in the tank.

【0013】[0013]

【発明の実施の形態】本発明の実施例について図1、2
により説明する。図1は培養槽10の断面を表わしてい
る。3枚羽根の2段プロペラで撹拌し、槽底に設置され
たリングスパージャー通気口4から通気を行っている。
1は上段のプロペラ翼を、2は下段のプロペラ翼を示
し、3は攪拌機13(図2)によって攪拌するプロペラ
1、2の回転軸である。また、運転条件は、液容量10
m3、撹拌回転数25rpm、通気量 0.03VVMである。本実
施例では槽の構造及び運転条件だけから溶存酸素濃度分
布を求めているので、どのような通気攪拌槽でも構造と
運転条件を決定すれば、溶存酸素濃度分布を計算する事
が可能である。例えば溶存酸素濃度分布klaは次式に
よって計算することができる。
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring to FIGS.
This will be described below. FIG. 1 shows a cross section of the culture tank 10. The mixture was stirred by a three-blade two-stage propeller and ventilated from a ring sparger vent 4 installed at the bottom of the tank.
Reference numeral 1 denotes an upper propeller blade, reference numeral 2 denotes a lower propeller blade, and reference numeral 3 denotes a rotating shaft of the propellers 1 and 2 which are stirred by a stirrer 13 (FIG. 2). The operating conditions are as follows:
m 3 , stirring speed: 25 rpm, ventilation volume: 0.03 VVM. In the present embodiment, the dissolved oxygen concentration distribution is obtained only from the structure and operating conditions of the tank, so that the dissolved oxygen concentration distribution can be calculated by determining the structure and operating conditions in any aeration and stirring tank. . For example, the dissolved oxygen concentration distribution kla can be calculated by the following equation.

【0014】kla=kl・a kl=0.301So2 -1/2(εν)1/4 a=3α/Rb ただし、 kl:液境膜移動係数(m/s) So2:酸素のシュミット数 (=ν/Do2) ε:乱流エネルギー散逸速度(m2/s3) ν:動粘度(m2/s) Do2:液相中の酸素の拡散係数(m2/s) a:単位体積当たりの気液接触面積(1/m) α:ガスホールドアップ Rb:気泡半径(m) 上記で求めたklaの分布を用いて、次の式を有限差分
法により計算することで、溶存酸素濃度分布を求めるこ
とができる。
Kla = kl · a kl = 0.301 S o2 -1/2 (εν) 1/4 a = 3α / Rb where kl: liquid film transfer coefficient (m / s) S o2 : oxygen Schmitt number ( = ν / D o2 ) ε: Turbulent energy dissipation rate (m 2 / s 3 ) ν: Kinematic viscosity (m 2 / s) D o2 : Diffusion coefficient of oxygen in liquid phase (m 2 / s) a: Unit Gas-liquid contact area per volume (1 / m) α: Gas hold-up Rb: Bubble radius (m) Using the distribution of kla obtained above, calculate the following equation by the finite difference method to obtain dissolved oxygen The concentration distribution can be determined.

【0015】 ∂C/∂t = -div(C・(Ux,Uy,Uz))+DO22C+kla(C*-C)+G ただし、 C :液中の溶存酸素濃度(mol/m3) (Ux,Uy,Uz) :流速ベクトル(m/s) kla :ガス移動容量係数(1/s) C* :飽和酸素濃度(mol/m3) (=p/H) p :水圧(atm) H :ヘンリー定数(atm・m3/mol) G :液中で単位体積・単位時間当たりに細胞が消費する
溶存酸素のモル数(mol/s・m3) 次に酸素濃度分布の計算を利用して制御を行う培養槽の
運転制御の実施例について述べる。通気培養槽に取り付
けた1つ以上の溶存酸素計12で溶存酸素を測定し信号
を電子計算機16に送る。電子計算機16では、まず通
気攪拌槽の構造及び運転条件を境界条件及び方程式の係
数として流れの数値解析をした結果からkla分布を求
め、そのkla分布を用いて溶存酸素濃度分布を計算す
る。その後、溶存酸素計12から信号として送られた溶
存酸素濃度で補正を行う。溶存酸素濃度の値が培養条件
からはずれた領域が存在した場合、電子計算機は攪拌回
転数、通気量、通気ガス中の酸素分圧、及び内圧のいず
れかもしくは全部を変更して溶存酸素濃度分布を計算し
直す。溶存酸素の最大値及び最小値が培養条件に適合す
る値が得られるまでパラメータの変更及び計算を繰り返
した後、攪拌機13、酸素分離器15、圧力調整器14
を操作して計算で求めた攪拌回転数、通気量、酸素分圧
及び内圧に実際の培養槽の運転条件を変更する。この操
作を続けることで溶存酸素濃度分布が最適な運転条件で
培養を行うことができる。
∂C / ∂t = −div (C · (Ux, Uy, Uz)) + D O22 C + kla (C * -C) + G where C: dissolved oxygen concentration in the liquid (mol / m 3 ) (Ux, Uy, Uz): Flow velocity vector (m / s) kla: Gas transfer capacity coefficient (1 / s) C * : Saturated oxygen concentration (mol / m 3 ) (= p / H) p: Water pressure (atm) H: Henry's constant (atm ・ m 3 / mol) G: Number of moles of dissolved oxygen consumed by cells per unit volume / time in liquid (mol / s ・ m 3 ) Next, oxygen concentration distribution An embodiment of the operation control of the culture tank in which the control is performed using the calculation of the above will be described. The dissolved oxygen is measured by one or more dissolved oxygen meters 12 attached to the aeration culture tank, and a signal is sent to the computer 16. The electronic computer 16 first obtains a kla distribution from the result of numerical analysis of the flow using the structure and operating conditions of the ventilation stirring tank as boundary conditions and coefficients of equations, and calculates a dissolved oxygen concentration distribution using the kla distribution. Thereafter, the correction is performed using the dissolved oxygen concentration sent as a signal from the dissolved oxygen meter 12. If there is a region where the dissolved oxygen concentration deviates from the cultivation conditions, the computer changes the stirring rotation speed, the amount of aeration, the oxygen partial pressure in the aerated gas, and / or all of the internal pressure to change the dissolved oxygen concentration distribution. Is recalculated. After repeatedly changing and calculating the parameters until the maximum and minimum values of the dissolved oxygen match the culture conditions, the stirrer 13, the oxygen separator 15, the pressure regulator 14
Is operated to change the actual operating conditions of the culture tank to the stirring rotation speed, the aeration amount, the oxygen partial pressure, and the internal pressure obtained by calculation. By continuing this operation, culturing can be performed under operating conditions in which the dissolved oxygen concentration distribution is optimal.

【0016】計算機16におけるこれらの処理フローの
例を図3に示す。ステップ30では溶存酸素計12から
の信号を取り込む。ステップ32ではガス移動容量係数
klaを計算し、そしてステップ30で取り込んだ溶存
酸素により補正する。この演算された溶存酸素濃度分布
の値が培養条件から外れた領域があるかどうかをステッ
プ34で判定し、外れている領域がある場合は、ステッ
プ36で攪拌回転数、通気量、通気ガス中の酸素分圧、
および内圧のいずれか、または全部を変更して溶存酸素
濃度分布を計算し直す。パラメータ変更計算を繰り返し
たあとで、実際の培養槽の運転条件をステップ38で変
更する。ステップ40では溶存酸素が所定の範囲内にあ
るかどうかを判断し、満足していれば処理を終了する。
満足していない場合はステップ32以降の処理を繰り返
す。このように予め定められた範囲に入るように制御す
ることによって、培養成生物の品質の向上にもつなが
る。
FIG. 3 shows an example of these processing flows in the computer 16. In step 30, a signal from the dissolved oxygen meter 12 is fetched. In step 32, the gas transfer capacity coefficient kla is calculated and corrected by the dissolved oxygen taken in step 30. It is determined in step 34 whether or not there is a region where the calculated value of the dissolved oxygen concentration distribution deviates from the cultivation conditions. Oxygen partial pressure,
Recalculate the dissolved oxygen concentration distribution by changing any or all of the internal pressure. After repeating the parameter change calculation, the actual operating conditions of the culture tank are changed in step 38. In step 40, it is determined whether or not the dissolved oxygen is within a predetermined range, and if satisfied, the process is terminated.
If not satisfied, the processing from step 32 on is repeated. By controlling so as to fall within the predetermined range, the quality of the cultured organism is improved.

【0017】また、溶存濃度が所定の範囲内にあるよう
にするガスは、酸素に限定されるものではなく、通気撹
拌培養槽内で消費され、または生成される結果として、
気泡から液中に溶け込むあるいは液中から気泡内に追い
出される溶質ガスであればどのようなものでも適用でき
る。具体的には図3と同様な計算を、高濃度になった場
合は菌の活動を阻害する二酸化炭素(菌の活動に伴い菌
から液中に放出される)について行うことで、溶存二酸
化炭素濃度分布を求めること及び溶存二酸化炭素濃度を
無害な濃度に保つよう培養槽を制御することも可能であ
る。
Further, the gas for controlling the dissolved concentration within the predetermined range is not limited to oxygen, but is consumed or generated in the aeration-stirred culture tank as a result.
Any solute gas can be applied as long as it is a solute gas that dissolves into the liquid from the bubbles or is expelled from the liquid into the bubbles. Specifically, the same calculation as in FIG. 3 is performed for carbon dioxide that inhibits the activity of bacteria when the concentration becomes high (discharged into the liquid from the bacteria along with the activity of the bacteria). It is also possible to determine the concentration distribution and to control the culture tank so as to keep the dissolved carbon dioxide concentration harmless.

【0018】物質の保存則を表す微分方程式を離散化し
て溶質ガス濃度分布を数値解析する方法であってもよ
い。例えば、(溶質ガス濃度の時間変化)=(流れによる溶
質ガスの流入流出量)+(拡散による溶質ガスの流入流出
量)+(気液間のガス移動量)+(溶質ガスが微生物や細胞の
活動又は化学反応により消費又は生成される量)、関係
を利用すればよい。
A method of numerically analyzing a solute gas concentration distribution by discretizing a differential equation representing a conservation law of a substance may be used. For example, (time change of solute gas concentration) = (inflow and outflow of solute gas due to flow) + (inflow and outflow of solute gas due to diffusion) + (gas transfer between gas and liquid) + (solute gas contains microorganisms and cells The amount consumed or generated by the activity or chemical reaction of the above) or the relationship may be used.

【0019】[0019]

【発明の効果】本発明によれば、従来不可能であった通
気撹拌槽内の溶質ガス濃度分布を構造及び運転条件だけ
から計算し、最適な値に制御することができる。したが
って、槽構造の変更や新規設計を行った場合に、実際の
槽を製作し溶質ガス濃度分布を測定することなく計算の
みで予測することが出来る。
According to the present invention, it is possible to calculate the solute gas concentration distribution in the aeration-stirring tank, which was impossible in the past, only from the structure and the operating conditions, and to control it to an optimum value. Therefore, when the tank structure is changed or a new design is made, it is possible to predict only by calculation without manufacturing an actual tank and measuring the solute gas concentration distribution.

【0020】また、本発明によれば通気撹拌槽内の全て
の点における溶質ガス濃度の最大値及び最小値が培養条
件に収まるように、運転条件を制御することが可能であ
るため、培養生産物の品質維持に効果がある。
Further, according to the present invention, since the operating conditions can be controlled so that the maximum and minimum values of the solute gas concentration at all points in the aeration and stirring tank fall within the culture conditions, the culture production is controlled. It is effective in maintaining the quality of goods.

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

【図1】本発明の一実施例の数値解析による2段プロペ
ラ翼を使用した通気撹拌槽の断面と溶存酸素濃度分布を
示す図である。
FIG. 1 is a diagram showing a cross section of a ventilation stirring tank using a two-stage propeller blade and a distribution of dissolved oxygen concentration by numerical analysis of an embodiment of the present invention.

【図2】本発明による通気撹拌培養槽の運転制御の一実
施例を示すブロック構成図である。
FIG. 2 is a block diagram showing one embodiment of the operation control of the aeration-stirred culture tank according to the present invention.

【図3】溶存酸素濃度分布計算を制御用電子計算機で行
なわせる場合の処理フロー図の一例を示す図である。
FIG. 3 is a diagram showing an example of a processing flow diagram in a case where a dissolved oxygen concentration distribution calculation is performed by a control computer.

【符号の説明】[Explanation of symbols]

1…上プロペラ翼、2…下プロペラ翼、3…軸、4…リン
グスパージャー通気口、10…培養槽、12…溶存酸素計
(一つ以上)、13…攪拌機、14…圧力調整器、15…
酸素分離器、16…制御用電子計算機
1 ... upper propeller blade, 2 ... lower propeller blade, 3 ... shaft, 4 ... ring sparger vent, 10 ... culture tank, 12 ... dissolved oxygen meter
(One or more), 13 ... stirrer, 14 ... pressure regulator, 15 ...
Oxygen separator, 16 ... electronic computer for control

───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 FI テーマコート゛(参考) C12M 1/36 C12M 1/36 (72)発明者 原田 進 山口県下松市大字東豊井794番地 株式会 社日立製作所笠戸事業所内 Fターム(参考) 4B029 AA02 BB01 CC01 DB01 DB11 DB12 DF04 DF08 DF10 4B065 BC05 BC06 BC08 BC12 BC14 BC18 CA60 ──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme court ゛ (Reference) C12M 1/36 C12M 1/36 (72) Inventor Susumu Harada 794, Higashi-Toyoi, Kazamatsu-shi, Yamaguchi Pref. F term in Hitachi Kasado Works (reference) 4B029 AA02 BB01 CC01 DB01 DB11 DB12 DF04 DF08 DF10 4B065 BC05 BC06 BC08 BC12 BC14 BC18 CA60

Claims (3)

【特許請求の範囲】[Claims] 【請求項1】通気攪拌培養槽内の溶質ガス濃度分布を最
適に制御する方法において、前記槽内の複数点で溶存酸
素濃度を計測し、前記槽のガス移動容量係数の分布を求
め、前記分布を用いて溶存酸素濃度分布を演算し、前記
計測された溶存酸素濃度を用いて前記溶存酸素濃度分布
を補正し、前記補正された溶存酸素濃度分布のうち培養
条件から外れている領域があるかどうかを判断し、培養
条件から外れている領域がある場合は溶存酸素濃度分布
があらかじめ定められた値になるまで前記培養槽の攪拌
回転数、通気量、通気ガス中の酸素分圧あるいは内圧を
調整することを特徴とする通気攪拌培養槽の運転制御方
法。
In a method for optimally controlling a solute gas concentration distribution in an aeration-stirred culture tank, a dissolved oxygen concentration is measured at a plurality of points in the tank, and a distribution of a gas transfer capacity coefficient in the tank is obtained. Calculate the dissolved oxygen concentration distribution using the distribution, correct the dissolved oxygen concentration distribution using the measured dissolved oxygen concentration, there is a region of the corrected dissolved oxygen concentration distribution that is out of the culture condition Judge whether or not there is a region that is out of the culturing conditions, until the dissolved oxygen concentration distribution reaches a predetermined value, the stirring rotation speed of the culturing tank, the aeration rate, the oxygen partial pressure or the internal pressure in the aerated gas. And controlling the operation of the aeration-stirred culture tank.
【請求項2】請求項1記載において、ガス移動容量係数
(kla)の分布を乱流エネルギー散逸速度、動粘度、
ガスホールドアップ、気泡半径、シュミット数の関数と
して求めることを特徴とする通気攪拌培養槽の運転制御
方法。
2. The method according to claim 1, wherein the distribution of the gas transfer capacity coefficient (kla) is determined by a turbulent energy dissipation rate, a kinematic viscosity,
A method for controlling operation of an aeration-stirred culture tank, wherein the method is obtained as a function of gas hold-up, bubble radius, and Schmidt number.
【請求項3】請求項2記載において、ガス移動容量係数
(kla)の分布を次の式から求めることを特徴とする
通気攪拌培養槽の運転制御方法。 kla=f(Sc,ε,ν,α,Rb) ただし、 kla:ガス移動容量係数(1/h) kl:液境膜移動係数(m/s) a :単位体積当たりの気液接触面積(1/m) Sc:シュミット数 (=ν/Dg) ε:乱流エネルギー散逸速度(m2/s3) ν:動粘度(m2/s) Dg:液相中のガスの拡散係数(m2/s) α :ガスホールドアップ Rb :気泡半径(m)
3. The method according to claim 2, wherein the distribution of the gas transfer capacity coefficient (kla) is obtained from the following equation. kla = f (Sc, ε, ν, α, Rb) where kla: gas transfer capacity coefficient (1 / h) kl: liquid film transfer coefficient (m / s) a: gas-liquid contact area per unit volume ( 1 / m) Sc: Schmidt number (= ν / Dg) ε: Turbulent energy dissipation rate (m 2 / s 3 ) ν: Kinematic viscosity (m 2 / s) Dg: Diffusion coefficient of gas in liquid phase (m 2 / s) α: Gas hold-up Rb: Bubble radius (m)
JP2000052312A 2000-02-24 2000-02-24 Operation control method of aeration and stirring culture tank Expired - Lifetime JP4103288B2 (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1705243A1 (en) * 2005-03-24 2006-09-27 Hitachi, Ltd. Control device for fermenter
JP2010124722A (en) * 2008-11-26 2010-06-10 Ihi Corp Measurement device and method, and apparatus and method for operating culture tank system
JP2019042615A (en) * 2017-08-30 2019-03-22 株式会社日立製作所 Mixer and mixing method
JP2019141797A (en) * 2018-02-21 2019-08-29 住友金属鉱山株式会社 Calculation method of gas-liquid interface area and position design method of gas blowing port

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1705243A1 (en) * 2005-03-24 2006-09-27 Hitachi, Ltd. Control device for fermenter
US7771988B2 (en) 2005-03-24 2010-08-10 Hitachi, Ltd. Control device for fermenter
JP2010124722A (en) * 2008-11-26 2010-06-10 Ihi Corp Measurement device and method, and apparatus and method for operating culture tank system
JP2019042615A (en) * 2017-08-30 2019-03-22 株式会社日立製作所 Mixer and mixing method
JP2019141797A (en) * 2018-02-21 2019-08-29 住友金属鉱山株式会社 Calculation method of gas-liquid interface area and position design method of gas blowing port
JP7006361B2 (en) 2018-02-21 2022-01-24 住友金属鉱山株式会社 Calculation method of gas-liquid boundary area and position design method of gas inlet

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