JPH0531332A - Membrane separation of microorganism - Google Patents
Membrane separation of microorganismInfo
- Publication number
- JPH0531332A JPH0531332A JP21267491A JP21267491A JPH0531332A JP H0531332 A JPH0531332 A JP H0531332A JP 21267491 A JP21267491 A JP 21267491A JP 21267491 A JP21267491 A JP 21267491A JP H0531332 A JPH0531332 A JP H0531332A
- Authority
- JP
- Japan
- Prior art keywords
- suspension
- membrane
- microorganism
- shear stress
- microbial suspension
- 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.)
- Withdrawn
Links
- 239000012528 membrane Substances 0.000 title claims abstract description 60
- 244000005700 microbiome Species 0.000 title claims abstract description 32
- 238000000926 separation method Methods 0.000 title claims description 22
- 239000000725 suspension Substances 0.000 claims abstract description 40
- 239000007788 liquid Substances 0.000 claims abstract description 7
- 230000000813 microbial effect Effects 0.000 claims description 30
- 241000588724 Escherichia coli Species 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 10
- 239000012466 permeate Substances 0.000 claims description 6
- 244000063299 Bacillus subtilis Species 0.000 claims description 5
- 235000014469 Bacillus subtilis Nutrition 0.000 claims description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 5
- 238000010008 shearing Methods 0.000 abstract description 3
- 239000002699 waste material Substances 0.000 abstract description 3
- 230000006378 damage Effects 0.000 abstract description 2
- 102000005936 beta-Galactosidase Human genes 0.000 description 6
- 108010005774 beta-Galactosidase Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 102000002464 Galactosidases Human genes 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明はバイオリアクターに膜分
離装置を組込んだ場合の処理方法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a treatment method when a membrane separation device is incorporated in a bioreactor.
【０００２】[0002]
【従来の技術】微生物を増殖したり濃縮するバイオリア
クターとして、培養槽内の微生物を含む培養液つまり微
生物懸濁液を循環ポンプによってクロスフロー式の膜モ
ジュール内の分離膜の一次側に供給し、微生物懸濁液を
分離膜の膜面に沿って平行に流し、分離膜の二次側に微
生物の増殖に伴って生成された増殖を阻害する不要成分
を含む液を透過させ、不要成分が除かれた微生物懸濁液
を再び培養槽に戻すようにしたものが知られている。2. Description of the Related Art As a bioreactor for growing or concentrating microorganisms, a culture solution containing microorganisms in a culture tank, that is, a microorganism suspension, is supplied to a primary side of a separation membrane in a cross-flow type membrane module by a circulation pump. , The microbial suspension is flown in parallel along the membrane surface of the separation membrane, and the secondary side of the separation membrane permeates a liquid containing unnecessary components that inhibits the growth generated along with the growth of microorganisms. It is known that the removed microbial suspension is returned to the culture tank again.
【０００３】[0003]
【発明が解決しようとする課題】上述したバイオリアク
ターにおいては、常に微生物懸濁液が培養槽と膜モジュ
ールとの間を循環しているため、微生物懸濁液に絶えず
剪断応力が作用している。そして、クロスフロー式の膜
モジュールにあっては膜面に沿って微生物懸濁液が流れ
るため、この膜面での剪断応力が大きく、またポンプで
微生物懸濁液を循環させる場合にはポンプ内、バルブ或
いは配管内における剪断応力も大きい。このため、剪断
応力によって微生物が破壊され失活することがある。In the bioreactor described above, since the microbial suspension is constantly circulated between the culture tank and the membrane module, the microbial suspension is constantly subjected to shear stress. . Further, in the cross-flow type membrane module, the microbial suspension flows along the membrane surface, so that the shear stress on this membrane surface is large, and when circulating the microbial suspension with a pump, The shear stress in the valve or pipe is also large. Therefore, the shear stress may destroy and deactivate the microorganisms.
【０００４】[0004]
【課題を解決するための手段】上記課題を解決すべく本
願の第１発明は、微生物懸濁液に加えられる剪断応力を
微生物懸濁液の粘度等の流動特性から算出し、この剪断
応力が個々の微生物に応じて設定した所定値を超えない
ように循環流量を制御するようにし、また本願の第２発
明は微生物の剪断破壊量を直接測定し、この剪断破壊量
が所定値を超えないように循環流量を制御するようにし
た。In order to solve the above-mentioned problems, the first invention of the present application is to calculate the shear stress applied to a microbial suspension from flow characteristics such as viscosity of the microbial suspension. The circulation flow rate is controlled so as not to exceed a predetermined value set according to each microorganism, and the second invention of the present application directly measures the shear fracture amount of the microorganism, and the shear fracture amount does not exceed the predetermined value. The circulation flow rate was controlled as described above.
【０００５】[0005]
【作用】微生物懸濁液に作用する剪断応力は例えば微生
物懸濁液の見掛けの粘度と剪断速度との積で表される。
ここで、剪断速度は循環流量に比例するため、粘度を知
ることができれば微生物懸濁液に作用する剪断応力を算
出することができ、算出した剪断応力が所定値よりも大
きければ循環流量を少なくすることで、剪断応力を所定
値以下に下げることができる。The shear stress acting on the microbial suspension is represented by, for example, the product of the apparent viscosity of the microbial suspension and the shear rate.
Here, since the shear rate is proportional to the circulation flow rate, if the viscosity can be known, the shear stress acting on the microbial suspension can be calculated, and if the calculated shear stress is larger than a predetermined value, the circulation flow rate is reduced. By doing so, the shear stress can be reduced to a predetermined value or less.
【０００６】[0006]
【実施例】以下に本発明の実施例を添付図面に基づいて
説明する。ここで、図１は本願の第１発明に係る膜分離
方法の実施に用いる膜処理装置の概略図であり、膜処理
装置は培養槽１内に微生物を混入した培養液すなわち微
生物懸濁液２を満たし、この微生物懸濁液２をモータ３
にて回転せしめられる攪拌機４にて攪拌するようにして
いる。Embodiments of the present invention will be described below with reference to the accompanying drawings. Here, FIG. 1 is a schematic view of a membrane treatment apparatus used for carrying out the membrane separation method according to the first invention of the present application. The membrane treatment apparatus is a culture solution in which a microorganism is mixed in a culture tank 1, that is, a microorganism suspension 2 The microbial suspension 2 and the motor 3
It is arranged to stir with a stirrer 4 which is rotated by.
【０００７】また、槽１の底部からは循環パイプ５を導
出し、ポンプ６にて微生物懸濁液２を膜モジュール７に
供給し、膜面に沿って微生物懸濁液２を流すことで不要
成分を含む液については膜を透過せしめ、老廃物や溶解
成分等の不要成分が除かれた微生物懸濁液２については
圧力調製バルブを備えた循環パイプ５を介して再び培養
槽１上部に戻すようにしている。Further, the circulation pipe 5 is led out from the bottom of the tank 1, the microbial suspension 2 is supplied to the membrane module 7 by the pump 6, and the microbial suspension 2 is flowed along the membrane surface, which is unnecessary. The liquid containing the components is permeated through the membrane, and the microbial suspension 2 from which unnecessary components such as waste products and dissolved components are removed is returned to the upper part of the culture tank 1 again via a circulation pipe 5 equipped with a pressure adjusting valve. I am trying.
【０００８】また培養槽１には微生物懸濁液２の粘度を
測定するレオメータ８を設け、このレオメータ８の測定
値を制御装置９に入力し、制御装置９では測定粘度に基
づき、ポンプ６を駆動するモータにオン・オフ信号或い
は回転数の制御信号を出力するようにしている。Further, the culture tank 1 is provided with a rheometer 8 for measuring the viscosity of the microbial suspension 2, and the measured value of the rheometer 8 is input to the control device 9. The control device 9 drives the pump 6 based on the measured viscosity. An on / off signal or a rotation speed control signal is output to the driving motor.
【０００９】図２は循環流量（膜面流速）を粘度に応じ
て変化せしめた本発明による実施例と一定の膜面流速と
した従来法による比較例とを菌体濃度と粘度において比
較したものである。ここで実施例及び比較例を以下に示
す。FIG. 2 is a comparison of cell concentration and viscosity between an example according to the present invention in which the circulation flow rate (membrane surface velocity) is changed according to viscosity and a comparative example by a conventional method with a constant membrane surface velocity. Is. Here, examples and comparative examples are shown below.
【００１０】（実施例）遺伝子組替え大腸菌によるβ−
ガラクトシダーゼの生産において、発酵液からβ−ガラ
クトシダーゼを抽出する前段階として大腸菌の濃縮を本
発明方法によって行なった。大腸菌はグラム陰性の微生
物であるため、発酵時に生産した物質を系内に蓄積する
性質がある。また発酵したβ−ガラクトシダーゼを精製
するには、系内にβ−ガラクトシダーゼを蓄積した大腸
菌を破壊しないよう濃縮後、破壊・精製する。大腸菌の
濃縮に用いた膜モジュールは日東電工製の精密濾過膜Ｎ
ＴＵ−２０２０とし、膜分離条件は温度２０℃、膜間差
圧１．０kg/cm2、膜面流速は２．０ｍ／ｓとした。膜分
離開始時の大腸菌の濃度は２．４ｇ／ｌであった。膜分
離開始後、濾過対象液中の大腸菌濃度の上昇とともに粘
度も上昇した。この粘度に伴う剪断応力の上昇が大腸菌
を破壊していることが透過液中のβ−ガラクトシダーゼ
濃度より推察されたので、膜面流速を循環ポンプのイン
バータ制御により低下させた。最終的に得られた大腸菌
の濃度は１２７．８ｇ／ｌとなり、その中から３６，８
００Ｕ／ｌの酵素が回収された。(Example) β-by recombinant E. coli
In the production of galactosidase, E. coli was concentrated by the method of the present invention as a step prior to extracting β-galactosidase from the fermentation broth. Since Escherichia coli is a Gram-negative microorganism, it has the property of accumulating substances produced during fermentation in the system. In order to purify the fermented β-galactosidase, the Escherichia coli accumulating β-galactosidase in the system is concentrated so as not to destroy it, and then destroyed and purified. The membrane module used to concentrate E. coli is a microfiltration membrane N manufactured by Nitto Denko.
TU-2020, the membrane separation conditions were a temperature of 20 ° C., a transmembrane pressure difference of 1.0 kg / cm 2 , and a membrane surface velocity of 2.0 m / s. The concentration of E. coli at the start of membrane separation was 2.4 g / l. After the start of membrane separation, the viscosity increased as the E. coli concentration in the liquid to be filtered increased. Since it was inferred from the β-galactosidase concentration in the permeate that the increase in shear stress due to this viscosity destroyed Escherichia coli, the membrane surface velocity was reduced by the inverter control of the circulation pump. The final concentration of E. coli was 127.8 g / l, of which 36,8
00 U / l of enzyme was recovered.
【００１１】（比較例）前記実施例に用いた膜分離装置
を用い、膜面流速を制御せずに他の条件は前記実施例と
同一にして大腸菌を濃縮した。膜分離開始時の大腸菌の
濃度は２．４ｇ／ｌであった。膜分離開始後、濾過対象
液中の大腸菌濃度の上昇とともに粘度も上昇した。この
粘度に伴う剪断応力の上昇が大腸菌を破壊していること
が透過液中のβ−ガラクトシダーゼ濃度より推察された
が、膜面流速の制御は行なわなかった。最終的に得られ
た大腸菌の濃度は９６．１ｇ／ｌとなり、その中から２
３，３００Ｕ／ｌの酵素が回収された。このように実施
例に比べ収率が低下したのは、膜分離操作中に大腸菌が
剪断応力の作用により破壊され、大腸菌内在のβ−ガラ
クトシダーゼが透過液側に流出したためと考えられる。(Comparative Example) Escherichia coli was concentrated using the membrane separation apparatus used in the above-mentioned Examples under the same conditions as in the above-mentioned Examples except that the flow velocity on the membrane surface was not controlled. The concentration of E. coli at the start of membrane separation was 2.4 g / l. After the start of membrane separation, the viscosity increased as the E. coli concentration in the liquid to be filtered increased. It was inferred from the β-galactosidase concentration in the permeate that the increase in shear stress accompanying the viscosity destroyed E. coli, but the flow velocity on the membrane was not controlled. The concentration of E. coli finally obtained was 96.1 g / l, of which 2
3,300 U / l of enzyme was recovered. It is considered that the reason why the yield was lower than that in Examples was that E. coli was destroyed by the action of shear stress during the membrane separation operation, and β-galactosidase contained in Escherichia coli flowed out to the permeate side.
【００１２】図３〜図５はそれぞれ酵母、大腸菌及び枯
草菌に対する剪断応力と破壊率との関係についての実験
結果を示すグラフである。これらのグラフから微生物の
剪断応力に対する耐性値は個々の微生物毎に異なり、酵
母は１．３ｋＮ／ｍ2、大腸菌は２．２ｋＮ／ｍ2、枯草
菌は３．０ｋＮ／ｍ2が剪断応力耐性値であることが判
明した。FIGS. 3 to 5 are graphs showing the results of experiments on the relationship between shear stress and fracture rate for yeast, Escherichia coli and Bacillus subtilis, respectively. Resistance values for the shear stress of microorganisms from these graphs differ for each individual microorganism, yeast 1.3kN / m 2, E. coli 2.2kN / m 2, Bacillus subtilis 3.0 kN / m 2 is the shear stress resistance It turned out to be a value.
【００１３】また、微生物の培養においては少なくとも
剪断力は破壊率が５０％以下となるものでなければなら
ない。このことを考慮すれば、酵母に加えられる剪断応
力は８，０００Ｎ／ｍ2を超えないように、大腸菌に加
えられる剪断応力は９，０００Ｎ／ｍ2を超えないよう
に、また枯草菌に加えられる剪断応力は１０，０００Ｎ
／ｍ2を超えないように循環流量（膜面流速）を制御す
べきである。Further, in culturing microorganisms, at least the shearing force must have a breaking rate of 50% or less. Taking this into consideration, the shear stress applied to the yeast so as not to exceed the 8,000N / m 2, the shear stress applied to the E. coli so as not to exceed the 9,000N / m 2, In addition to Bacillus subtilis Shear stress is 10,000N
The circulation flow rate (membrane surface flow velocity) should be controlled so as not to exceed / m 2 .
【００１４】図６は第２発明に係る膜分離方法の実施に
用いる装置の概略図であり、この装置にあっては前記第
１発明ではレオメータ８を用いて微生物懸濁液の粘度を
測定し、この粘度から剪断応力を算出し、剪断応力と破
壊率との関係から循環流量を制御するようにしていた
が、この第２発明にあっては酵素等を組込んだ検出器１
０で直接微生物の破壊量を測定し、この測定値を制御装
置９に入力してポンプの循環流量を制御するようにして
いる。このようにした場合、第１発明の方法よりも対応
に遅れが多少生じるが正確な制御が可能になる。FIG. 6 is a schematic view of an apparatus used for carrying out the membrane separation method according to the second invention. In this apparatus, the rheometer 8 in the first invention is used to measure the viscosity of a microbial suspension. The shear stress was calculated from this viscosity, and the circulating flow rate was controlled from the relationship between the shear stress and the fracture rate. In the second invention, however, the detector 1 incorporating an enzyme or the like was used.
The amount of destruction of microorganisms is directly measured at 0, and the measured value is input to the control device 9 to control the circulating flow rate of the pump. In such a case, accurate control can be performed although a slight delay occurs in correspondence with the method of the first aspect of the invention.
【００１５】[0015]
【発明の効果】以上に説明した如く本発明によれば、微
生物の膜分離方法における懸濁液の循環流量を制御して
微生物に対する剪断応力が所定値を超えないようにした
ので、微生物の増殖を効果的に行なうことができ、特に
当該剪断応力を微生物懸濁液の粘度からオンラインで算
出するようにすれば、リアルタイムで制御遅れのない微
生物増殖の自動運転が可能となる。As described above, according to the present invention, since the circulation flow rate of the suspension in the method for separating a membrane of microorganisms is controlled so that the shear stress on the microorganisms does not exceed a predetermined value, the growth of microorganisms is prevented. When the shear stress is calculated online from the viscosity of the microbial suspension, the microbial growth can be automatically operated in real time without delay in control.
【図１】本願の第１発明に係る膜分離方法の実施に用い
る膜分離装置の概略図FIG. 1 is a schematic view of a membrane separation apparatus used for carrying out a membrane separation method according to a first invention of the present application.
【図２】本発明方法と従来法によって菌株を培養した場
合の膜分離時間と膜面流速、微生物懸濁液の粘度、菌体
濃度との関係を示すグラフFIG. 2 is a graph showing the relationship between the membrane separation time, the membrane surface flow velocity, the viscosity of the microbial suspension, and the bacterial cell concentration when the strains were cultured by the method of the present invention and the conventional method.
【図３】酵母に対する剪断応力と破壊率との関係を示す
グラフFIG. 3 is a graph showing the relationship between shear stress and fracture rate for yeast.
【図４】大腸菌に対する剪断応力と破壊率との関係を示
すグラフFIG. 4 is a graph showing the relationship between shear stress and fracture rate for E. coli.
【図５】枯草菌に対する剪断応力と破壊率との関係を示
すグラフFIG. 5 is a graph showing the relationship between shear stress and fracture rate against Bacillus subtilis.
【図６】本願の第２発明に係る膜分離方法の実施に用い
る膜処理装置の概略図FIG. 6 is a schematic diagram of a membrane processing apparatus used for carrying out a membrane separation method according to a second invention of the present application.
１…培養槽、２…微生物懸濁液、５…循環パイプ、６…
ポンプ、７…膜モジュール、８…レオメータ、９…制御
装置。1 ... Culture tank, 2 ... Microbial suspension, 5 ... Circulation pipe, 6 ...
Pump, 7 ... Membrane module, 8 ... Rheometer, 9 ... Control device.
Claims (5)
濁液を取り出して膜モジュールに供給し、この膜モジュ
ールの膜面に沿って微生物懸濁液を流し、不要成分を含
む液を透過液として分離し、不要成分が除去された微生
物懸濁液を再び培養槽に戻すか回収するようにした微生
物の膜分離方法において、前記膜モジュールの膜面、循
環ポンプ内、バルブ或いは管路内において微生物懸濁液
に加えられる剪断応力を微生物懸濁液の粘度等の流動特
性から算出し、この剪断応力が所定値を超えないように
循環流量を制御するようにしたことを特徴とする微生物
の膜分離方法。1. A microbial suspension is taken out from a culture tank by a circulation pump and supplied to a membrane module, the microbial suspension is flown along the membrane surface of the membrane module, and a liquid containing unnecessary components is separated as a permeate. In the method for separating a microbial membrane in which the microbial suspension from which unnecessary components have been removed is returned to the culture tank or recovered, the microbial suspension is carried out on the membrane surface of the membrane module, the circulation pump, the valve or the pipeline. Shear stress applied to suspension is calculated from flow characteristics such as viscosity of microbial suspension, and circulation flow rate is controlled so that this shear stress does not exceed a specified value. Method.
濁液に加えられる剪断応力は８，０００Ｎ／ｍ2を超え
ないように循環流量を制御するようにした請求項１に記
載の微生物の膜分離方法。2. The microorganism according to claim 1, wherein the microorganism is yeast, and the circulation flow rate is controlled so that the shear stress applied to the microorganism suspension does not exceed 8,000 N / m 2 . Membrane separation method.
懸濁液に加えられる剪断応力は９，０００Ｎ／ｍ2を超
えないように循環流量を制御するようにした請求項１に
記載の微生物の膜分離方法。3. The microorganism according to claim 1, wherein the microorganism is Escherichia coli, and the circulation flow rate is controlled so that the shear stress applied to the microorganism suspension does not exceed 9,000 N / m 2 . Membrane separation method.
懸濁液に加えられる剪断応力は１０，０００Ｎ／ｍ2を
超えないように循環流量を制御するようにした請求項１
に記載の微生物の膜分離方法。4. The circulation flow rate is controlled so that the microorganism is Bacillus subtilis and the shear stress applied to the microorganism suspension does not exceed 10,000 N / m 2.
The method for separating a membrane of a microorganism according to 1.
濁液を取り出して膜モジュールに供給し、この膜モジュ
ールの膜面に沿って微生物懸濁液を流し、不要成分を含
む液を透過液として分離し、不要成分が除去された微生
物懸濁液を再び培養槽に戻すか回収するようにした微生
物の膜分離方法において、前記微生物の剪断破壊量を測
定し、この剪断破壊量が所定値を超えないように循環流
量を制御するようにしたことを特徴とする微生物の膜分
離方法。5. A microbial suspension is taken out from a culture tank by a circulation pump and supplied to a membrane module, the microbial suspension is flown along the membrane surface of the membrane module, and a liquid containing an unnecessary component is separated as a permeate. Then, in the method of membrane separation of microorganisms, which is to return the microbial suspension from which unnecessary components have been removed back to the culture tank or to collect it, the shear fracture amount of the microorganisms is measured, and the shear fracture amount exceeds a predetermined value. A method for membrane separation of microorganisms, characterized in that the circulation flow rate is controlled so as not to exist.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21267491A JPH0531332A (en) | 1991-07-30 | 1991-07-30 | Membrane separation of microorganism |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21267491A JPH0531332A (en) | 1991-07-30 | 1991-07-30 | Membrane separation of microorganism |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0531332A true JPH0531332A (en) | 1993-02-09 |
Family
ID=16626526
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21267491A Withdrawn JPH0531332A (en) | 1991-07-30 | 1991-07-30 | Membrane separation of microorganism |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0531332A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6773913B2 (en) | 2001-03-06 | 2004-08-10 | Sakae Arakaki | Device and process for purifying vectors |
| JP2009045037A (en) * | 2007-08-22 | 2009-03-05 | Asahi Breweries Ltd | Yeast feeder |
| JP2011036146A (en) * | 2009-08-07 | 2011-02-24 | Toray Ind Inc | Method for producing chemical by continuous culture and apparatus for producing the same |
| JP2012165764A (en) * | 2006-07-14 | 2012-09-06 | Dsm Ip Assets Bv | Improved process for culturing cell |
| JP2019122293A (en) * | 2018-01-16 | 2019-07-25 | 月島機械株式会社 | Culture apparatus |
-
1991
- 1991-07-30 JP JP21267491A patent/JPH0531332A/en not_active Withdrawn
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6773913B2 (en) | 2001-03-06 | 2004-08-10 | Sakae Arakaki | Device and process for purifying vectors |
| JP2012165764A (en) * | 2006-07-14 | 2012-09-06 | Dsm Ip Assets Bv | Improved process for culturing cell |
| JP2014217395A (en) * | 2006-07-14 | 2014-11-20 | ディーエスエム アイピー アセッツ ビー．ブイ． | Improved process for culturing cells |
| US9469865B2 (en) | 2006-07-14 | 2016-10-18 | Dpx Holdings B.V. | Process for the culturing of cells |
| JP2009045037A (en) * | 2007-08-22 | 2009-03-05 | Asahi Breweries Ltd | Yeast feeder |
| JP2011036146A (en) * | 2009-08-07 | 2011-02-24 | Toray Ind Inc | Method for producing chemical by continuous culture and apparatus for producing the same |
| JP2019122293A (en) * | 2018-01-16 | 2019-07-25 | 月島機械株式会社 | Culture apparatus |
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Legal Events
| Date | Code | Title | Description |
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| A300 | Withdrawal of application because of no request for examination |
Free format text: JAPANESE INTERMEDIATE CODE: A300 Effective date: 19981008 |