JP5500618B2 - Bubble detection method and defoaming device for reaction liquid - Google Patents

Bubble detection method and defoaming device for reaction liquid Download PDF

Info

Publication number
JP5500618B2
JP5500618B2 JP2009069053A JP2009069053A JP5500618B2 JP 5500618 B2 JP5500618 B2 JP 5500618B2 JP 2009069053 A JP2009069053 A JP 2009069053A JP 2009069053 A JP2009069053 A JP 2009069053A JP 5500618 B2 JP5500618 B2 JP 5500618B2
Authority
JP
Japan
Prior art keywords
reaction
reaction liquid
liquid surface
reaction vessel
bubbles
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.)
Active
Application number
JP2009069053A
Other languages
Japanese (ja)
Other versions
JP2010220499A (en
Inventor
正浩 高橋
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Meiji Co Ltd
Original Assignee
Meiji Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Meiji Co Ltd filed Critical Meiji Co Ltd
Priority to JP2009069053A priority Critical patent/JP5500618B2/en
Publication of JP2010220499A publication Critical patent/JP2010220499A/en
Application granted granted Critical
Publication of JP5500618B2 publication Critical patent/JP5500618B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

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
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/02—Means for regulation, monitoring, measurement or control, e.g. flow regulation of foam

Description

この発明は、反応工程で反応液の表面に気泡が発生する種々の化学反応において、反応液面での気泡の発生の有無や実際の発生量を機械的に自動化して検知する方法と、その方法を用いて、消泡剤の添加の時期や実際の添加量を、機械的に自動化して的確に制御する装置（システム）に関する。  The present invention relates to a method of mechanically automating and detecting the presence or absence of bubbles on the reaction liquid surface and the actual generation amount in various chemical reactions in which bubbles are generated on the surface of the reaction liquid in the reaction step, The present invention relates to an apparatus (system) that uses a method to accurately control the timing of addition of an antifoaming agent and the actual addition amount by mechanical automation.

種々の化学反応においては反応工程で反応液の表面に気泡が発生するものがある。この場合、反応液及び／又は気泡が反応槽から外側に溢れ出すことなどを防止するため、消泡剤を適宜添加するなどの消泡処理が必要になる。   In various chemical reactions, there are those in which bubbles are generated on the surface of the reaction solution in the reaction step. In this case, in order to prevent the reaction liquid and / or air bubbles from overflowing from the reaction tank, an antifoaming treatment such as adding an antifoaming agent as appropriate is necessary.

例えば、好気性培養による連続的な長時間の発酵工程などでは、空気や酸素を培養器内の培養液中に直接注入して（吹き込んで）、培養液中の溶存酸素濃度を所定の範囲に保持している。このとき、その注入した空気や酸素により、培養液面（上面）に大量の気泡が発生して、培養液及び／又は気泡が培養器外に溢れ出てしまうことがある。気泡の発生により培養液及び／又は気泡が培養器外に溢れ出てしまうと、培養物（発酵生産物）の収率の低下や培養器に付随する装置の汚染など、滅菌性、洗浄性、作業性などの面で問題が生じる。   For example, in a continuous long-time fermentation process by aerobic culture, air or oxygen is directly injected (blown) into the culture solution in the incubator, and the dissolved oxygen concentration in the culture solution is kept within a predetermined range. keeping. At this time, a large amount of air bubbles may be generated on the culture liquid surface (upper surface) due to the injected air or oxygen, and the culture liquid and / or air bubbles may overflow outside the incubator. When the culture fluid and / or bubbles overflow outside the incubator due to the generation of bubbles, sterilization, detergency, etc., such as a decrease in the yield of the culture (fermented product) and contamination of the devices associated with the incubator, Problems arise in terms of workability.

この問題に対する方策として、一般的には、反応液中へ消泡剤を添加することで、気泡の発生を抑制し、連続的な長時間の反応工程を安定化させる手法が採用されている。   As a measure against this problem, generally, a method of suppressing the generation of bubbles and stabilizing a continuous long-time reaction process by adding an antifoaming agent to the reaction solution is employed.

反応液中へ消泡剤を添加するにあたり、反応液面での気泡の発生の有無や、実際の発生量を検知すべく、以前から種々の手法が試みられている。   In adding an antifoaming agent to the reaction solution, various techniques have been tried for some time to detect the presence or absence of bubbles on the reaction solution surface and the actual generation amount.

例えば、フロート式（特許文献１、２）、電気伝導式（特許文献３〜８）、静電容量式（特許文献３、４、１０）、超音波式（特許文献１１）、温度式（特許文献１２）などによる、反応容器内の気泡や液面を検知する方法がある。これらの場合、何れも反応容器内にセンサーなどの設備（構造物）を設置する必要があり、前記した通り、滅菌性・洗浄性・作業性などで問題が発生しやすくなる。特に、電気伝導式や静電容量式では、実際に消泡した後に、固形物がセンサーに付着して、誤作動の発生が著しくなるおそれがあった。   For example, float type (Patent Literatures 1 and 2), electric conduction type (Patent Literatures 3 to 8), capacitance type (Patent Literatures 3, 4, and 10), ultrasonic type (Patent Literature 11), temperature type (patent There is a method for detecting bubbles or liquid level in a reaction vessel according to the literature 12). In any of these cases, it is necessary to install a sensor (equipment) such as a sensor in the reaction vessel, and as described above, problems are likely to occur due to sterilization, cleaning, workability, and the like. In particular, in the electric conduction type and the capacitance type, there is a possibility that the solid matter adheres to the sensor after the defoaming actually occurs, and the occurrence of malfunction becomes significant.

その他、特許文献１３では、液面の透過光の強度を検知して、画像処理で液面を検知する方法が提案されている。   In addition, Patent Document 13 proposes a method of detecting the intensity of transmitted light on the liquid level and detecting the liquid level by image processing.

特許文献１４では、培養槽の排気出口に気液分離装置を取り付け、その気液分離装置の通気出口にミスト分離装置を取り付けて、そのミスト分離装置の入口配管、戻り配管、本体などに、気泡の検知用センサーを取り付けた培養装置が提案されている。この装置では、気液分離装置とミスト分離装置の間に、回転体で気泡を叩くか遠心憤霧する、消泡装置を取り付ける機構も提案されている。   In Patent Document 14, a gas-liquid separation device is attached to an exhaust outlet of a culture tank, a mist separation device is attached to an aeration outlet of the gas-liquid separation device, and bubbles are formed in an inlet pipe, a return pipe, a main body, and the like of the mist separation apparatus. A culture apparatus equipped with a detection sensor has been proposed. In this apparatus, a mechanism for attaching a defoaming device is also proposed between the gas-liquid separation device and the mist separation device.

特許文献１５では、培養槽の排気出口に気液分離装置を取り付け、その気液分離装置の入口配管、戻り配管、本体などに、気泡の検知用センサーを取り付け、一方で、その気液分離装置の入口配管に、超音波発振ホーンを取り付けた培養装置が提案されている。   In Patent Document 15, a gas-liquid separator is attached to an exhaust outlet of a culture tank, and a bubble detection sensor is attached to an inlet pipe, a return pipe, a main body, and the like of the gas-liquid separator. Has been proposed in which an ultrasonic oscillating horn is attached to the inlet pipe of the above.

特許文献１６では 、培養槽に気泡の検知用センサーを取り付け、そのセンサーが発泡を検知すると、培養槽の気相部へ自動的に空気か水蒸気を吹き込んで消泡する培養装置が提案されている。   Patent Document 16 proposes a culture apparatus in which a bubble detection sensor is attached to a culture tank, and when the sensor detects foaming, air or water vapor is automatically blown into the gas phase portion of the culture tank to eliminate the bubbles. .

このような従来の方式やメカニズムでは、反応液面での気泡の発生の有無や、実際の発生量を機械的に自動化して正確に検知する上で改善すべき余地があった。すなわち、前述した従来の方式やメカニズムでは、消泡剤の添加の時期（タイミング）や実際の添加量を、機械的に自動化して的確に制御する上で改善すべき余地があった。   In such a conventional method and mechanism, there is room for improvement in accurately detecting the presence or absence of bubbles on the reaction liquid surface and the actual amount generated by mechanical automation. That is, in the above-described conventional methods and mechanisms, there is room for improvement in accurately controlling the timing (timing) of addition of the antifoaming agent and the actual addition amount by mechanical automation.

このため、従来の方式では、例えば、反応液面での気泡の発生の有無や実際の発生量を作業員（オペレーター）が人為的に確認しながら、消泡剤の添加の時期や実際の添加量を経験的に制御せざるを得ないという事態になることがあった。   For this reason, in the conventional method, for example, the presence or absence of bubbles on the reaction liquid surface and the actual amount generated are checked manually by the operator (operator) while the antifoaming agent is added and the actual addition There were times when the amount had to be controlled empirically.

特開平０７−２５３３４８号公報Japanese Patent Application Laid-Open No. 07-253348 特開２００４−１１４１８１号公報JP 2004-114181 A 特開平０２−１２８１２１号公報Japanese Patent Laid-Open No. 02-128121 特開昭６３−２９０９２０号公報JP-A-63-290920 特開平０３−０４８１２５号公報Japanese Patent Laid-Open No. 03-048125 特開平０２−０８６７６３号公報JP 02-086763 A 特開平０４−０２４４９８号公報Japanese Unexamined Patent Publication No. 04-024498 特開２００８−０２６２２０号公報JP 2008-026220 A 実用新案登録第２５８０２００号公報Utility Model Registration No. 2580200 特開平０４−３３１２０２号公報JP 04-331202 A 特開平１０−３３２４５９号公報Japanese Patent Laid-Open No. 10-332459 特開平１１−００９８８２号公報Japanese Patent Laid-Open No. 11-009882 特開平０７−１２０２９２号公報Japanese Patent Laid-Open No. 07-120292 特開平０５−１４６２８６号公報JP 05-146286 A 特開２００２−０５１７６３号公報JP 2002-051763 A 特開２００３−００９８４３号公報JP 2003-009843 A

この発明は、反応工程で反応液の表面に気泡が発生する種々の化学反応において、反応液面での気泡の発生の有無や実際の発生量を、機械的に自動化して検知する方法と、その方法を用いて、消泡剤の添加の時期や実際の添加量を、機械的に自動化して的確に制御する装置（システム）を提案することを目的にしている。   This invention is a method of mechanically automating and detecting the presence or absence and actual generation amount of bubbles on the reaction liquid surface in various chemical reactions in which bubbles are generated on the surface of the reaction liquid in the reaction step; The purpose is to propose an apparatus (system) that uses the method to mechanically automate and accurately control the timing of addition of the antifoaming agent and the actual addition amount.

本願の請求項１記載の発明は、
反応工程で気泡を発生させる反応液を収容している反応容器内の反応液面と、前記反応容器の内壁面との間の境界部分であって前記反応液面より上側において前記反応液面に近接する位置の前記反応容器の前記内壁面、又は、反応液面と、前記反応液内に挿入されている撹拌軸との間の境界部分であって前記反応液面より上側において前記反応液面に近接する位置の前記撹拌軸を前記反応容器の外から前記反応容器のサイトグラスを介して連続的に撮影し、当該連続的に撮影して得た連続画像情報を数値化した連続画像数値情報の変動により、前記反応液表面での気泡発生の有無及び／又は気泡発生量を検知する反応液の気泡検知方法であって、
前記撮影している前記内壁面、又は、前記撹拌軸における反応開始前に把握した画像情報を数値化した数値から、反応開始後に把握した画像情報を数値化した数値が、予め定めてある数値範囲変動することにより、前記連続画像数値情報の変動を判定することを特徴とする反応液の気泡検知方法
である。 The invention according to claim 1 of the present application is
It is a boundary part between the reaction liquid surface in the reaction container containing the reaction liquid that generates bubbles in the reaction step and the inner wall surface of the reaction container, and is above the reaction liquid surface and on the reaction liquid surface . The inner wall surface of the reaction vessel at a close position or a boundary portion between the reaction liquid surface and the stirring shaft inserted into the reaction liquid, and the reaction liquid surface above the reaction liquid surface Continuous image numerical information obtained by continuously imaging the stirring shaft at a position close to the outside through the sight glass of the reaction container from the outside of the reaction container and digitizing the continuous image information obtained by the continuous imaging the variation, detect the presence and / or the bubble generation of the bubble generation in the reaction liquid surface a reaction solution of the bubble detection method,
A numerical value range in which a numerical value obtained by quantifying the image information obtained after the start of the reaction from a numerical value obtained by quantifying the image information obtained before the start of the reaction on the inner wall surface or the stirring shaft is set in advance. It is a method for detecting bubbles in a reaction liquid, wherein the change in the continuous image numerical information is determined by changing .

請求項２の発明は、
前記連続画像情報に含まれるＨ（色相）、Ｓ（彩度）、Ｖ（明度）をそれぞれ数値化した前記連続画像数値情報の中の少なくとも一種を用いて前記連続画像数値情報の変動を判定することを特徴とする請求項１記載の反応液の気泡検知方法
である。 The invention of claim 2
The variation of the continuous image numerical information is determined using at least one of the continuous image numerical information obtained by digitizing H (hue), S (saturation), and V (lightness) included in the continuous image information. The method for detecting bubbles in a reaction liquid according to claim 1.

本願の請求項３記載の発明は、
反応工程で気泡を発生させる反応液を収容している反応容器と、
前記反応容器内の前記反応液に消泡剤を添加する消泡剤添加手段と、
前記反応容器内の反応液面と、前記反応容器の内壁面との間の境界部分であって前記反応液面より上側において前記反応液面に近接する位置の前記反応容器の内壁面、又は、反応液面と、前記反応液内に挿入されている撹拌軸との間の境界部分であって前記反応液面より上側において前記反応液面に近接する位置の前記撹拌軸を前記反応容器の外から前記反応容器のサイトグラスを介して連続的に撮影する撮像手段と、
前記撮像手段で連続的に撮影して得た連続画像情報を数値化した連続画像数値情報の変動により、前記反応液表面での気泡発生の有無及び／又は気泡発生量を検知し、前記消泡剤添加手段による前記反応容器内への消泡剤の添加開始及び添加中止を制御する制御手段と
を備えている消泡装置であって、
前記制御装置は、前記撮影している前記内壁面、又は、前記撹拌軸における反応開始前に把握した画像情報を数値化した数値から、反応開始後に把握した画像情報を数値化した数値が、予め定めてある数値範囲変動することにより、前記連続画像数値情報の変動を判定する
ことを特徴とする消泡装置
である。 Invention of Claim 3 of this application is
A reaction vessel containing a reaction solution that generates bubbles in the reaction process;
An antifoaming agent adding means for adding an antifoaming agent to the reaction solution in the reaction vessel;
The inner wall surface of the reaction vessel at a position near the reaction liquid surface above the reaction liquid surface, which is a boundary portion between the reaction liquid surface in the reaction vessel and the inner wall surface of the reaction vessel , or The stirring shaft at a position close to the reaction liquid surface at a boundary portion between the reaction liquid surface and the stirring shaft inserted into the reaction liquid and above the reaction liquid surface is disposed outside the reaction vessel. Imaging means for continuously photographing through the sight glass of the reaction vessel,
The presence / absence of bubbles on the reaction liquid surface and / or the amount of bubbles generated is detected based on fluctuations in the continuous image numerical information obtained by digitizing the continuous image information obtained by continuously photographing with the imaging means, and the defoaming is performed. A defoaming device comprising: control means for controlling the start and stop of addition of the antifoaming agent into the reaction vessel by the agent addition means ,
From the numerical value obtained by quantifying the image information obtained before the start of the reaction on the inner wall surface or the stirring shaft, the control device previously obtains a numerical value obtained by quantifying the image information obtained after the start of the reaction. The variation of the numerical value information of the continuous image is determined by changing the predetermined numerical range.
This is a defoaming device .

本願の請求項４記載の発明は、
前記制御装置は、前記連続画像情報に含まれるＨ（色相）、Ｓ（彩度）、Ｖ（明度）をそれぞれ数値化した前記連続画像数値情報の中の少なくとも一種を用いて、前記連続画像数値情報の変動を判定することを特徴とする請求項３記載の消泡装置
である。 Invention of Claim 4 of this application is
The control device uses the continuous image numerical value by using at least one of the continuous image numerical information obtained by digitizing H (hue), S (saturation), and V (brightness) included in the continuous image information. The defoaming device according to claim 3 , wherein a change in information is determined.

この発明によれば、反応工程で反応液の表面に気泡が発生する種々の化学反応において、反応液面での気泡の発生の有無や実際の発生量を、機械的に自動化して検知し、消泡剤の添加の時期や実際の添加量を、機械的に自動化して的確に制御することができる。   According to the present invention, in various chemical reactions in which bubbles are generated on the surface of the reaction liquid in the reaction step, the presence or absence of bubbles on the reaction liquid surface and the actual generation amount are mechanically automated and detected, The timing of adding the antifoaming agent and the actual amount added can be accurately controlled by mechanical automation.

本発明の方法が実施される本発明の消泡装置の一例の概略構成を説明する図。The figure explaining schematic structure of an example of the defoaming apparatus of this invention with which the method of this invention is implemented.

本発明においては、反応工程で気泡を発生させる反応液を収容している反応容器内の反応液面上に近接する位置の前記反応容器の構造物を前記反応容器の外から前記反応容器のサイトグラス（のぞき窓）を介して連続的に撮影する。そして、前記連続的に撮影して得た連続画像情報を数値化した連続画像数値情報の変動により前記反応液表面での気泡発生の有無及び／又は気泡発生量を検知している。   In the present invention, the structure of the reaction vessel at a position close to the surface of the reaction solution in the reaction vessel containing the reaction solution that generates bubbles in the reaction step is removed from the reaction vessel to the site of the reaction vessel. Shoot continuously through a glass (view window). The presence / absence of bubbles on the surface of the reaction liquid and / or the amount of bubbles generated is detected based on fluctuations in the continuous image numerical information obtained by digitizing the continuous image information obtained by the continuous photographing.

連続的な撮影には種々の撮像手段、例えば、ＣＣＤカメラなどを用いることができる。   Various imaging means such as a CCD camera can be used for continuous shooting.

前記において、反応容器内の反応液面上に近接する位置の前記反応容器の構造物とは、例えば、反応容器の内壁面や、反応液内に挿入されている攪拌軸のことである。   In the above, the structure of the reaction container at a position close to the reaction liquid surface in the reaction container is, for example, an inner wall surface of the reaction container or a stirring shaft inserted in the reaction liquid.

反応容器内の反応液面と、反応容器の内壁面との間の境界部分や、反応容器内の反応液面と、反応液内に挿入されている攪拌軸との間の境界部分であって、反応液面より上側において反応液面に近接する位置を観察することにより、反応工程で液面に気泡が発生したことを画像情報の変動として把握するものである。   A boundary portion between the reaction liquid surface in the reaction vessel and the inner wall surface of the reaction vessel, or a boundary portion between the reaction liquid surface in the reaction vessel and the stirring shaft inserted in the reaction solution. By observing a position close to the reaction liquid surface above the reaction liquid surface, it is grasped as variation in image information that bubbles are generated on the liquid surface in the reaction process.

この際、反応容器内の反応液面上に近接する位置を、反応工程の開始前や、必要に応じて反応工程の進行中に、反応容器内の反応液面より２０ｃｍ上の反応容器の内壁面、あるいは、反応容器内の反応液面より３０ｃｍ上の反応容器の内壁面などと任意に設定することができる。これによって、気泡の発生量がどの程度になった段階で、気泡が発生した状態であると検知するのかを任意に設定することができ、反応液面の気泡の発生量の許容範囲を自由に制御できる。   At this time, the position close to the reaction liquid level in the reaction vessel is set within the reaction vessel 20 cm above the reaction liquid level in the reaction vessel before the start of the reaction step or during the progress of the reaction step as necessary. It can be arbitrarily set as the wall surface or the inner wall surface of the reaction vessel 30 cm above the reaction liquid level in the reaction vessel. As a result, it is possible to arbitrarily set the level at which bubbles are generated, and to detect whether bubbles are generated. Can be controlled.

予め設定した、反応容器内の反応液面より所定の高さで上方の反応容器の内壁面、あるいは、反応容器内の反応液面より所定の高さで上方の攪拌軸を、反応工程の開始前に（すなわち、まだ気泡が発生していない状態で）前述した撮像手段により撮影し、この撮影して得た画像情報を数値化して制御手段に記録しておく。   Start the reaction process by setting the inner wall of the reaction vessel at a predetermined height above the reaction liquid level in the reaction vessel or the stirring shaft above the reaction liquid level in the reaction vessel at a predetermined height Before (that is, in a state in which no bubbles are generated), the image is taken by the above-described image pickup means, and the image information obtained by the image pickup is digitized and recorded in the control means.

一方、反応工程が開始された後、前記の予め設定されている測定箇所を連続的に撮影し、この撮影して得た連続画像情報を数値化した連続画像数値情報が、前記の反応の開始前に把握していた数値情報から所定の大きさで離れたことをもって、反応液表面での気泡発生の有無及び／又は気泡発生量を検知することができる。   On the other hand, after the reaction process is started, continuous image numerical information obtained by continuously photographing the preset measurement points and digitizing the continuous image information obtained by the photographing is the start of the reaction. The presence / absence of bubbles on the reaction liquid surface and / or the amount of bubbles generated can be detected by deviating by a predetermined size from the numerical information previously grasped.

例えば、好気性培養による連続的な長時間の発酵工程において、培養器（反応容器）内の培養液面と、内壁面や撹拌軸などとの境界部分を、培養器外からサイトグラスを通してＣＣＤカメラで連続的に撮影し、その画像情報をコンピューターで処理（モニター）する。これによって、培養液面での気泡の発生の有無や 実際の発生量を、機械的に 自動化して正確に検知するものである。   For example, in a continuous long-time fermentation process by aerobic culture, a CCD camera passes through the sight glass from the outside of the incubator to the boundary between the culture liquid level in the incubator (reaction vessel) and the inner wall surface and stirring shaft. Take pictures continuously with, and process (monitor) the image information with a computer. In this way, the presence or absence of bubbles on the culture surface and the actual amount of bubbles generated can be detected mechanically and accurately.

ここで、ＣＣＤカメラにより連続的に撮影して得た連続画像情報を数値化した連続画像数値情報の変動による反応液表面での気泡発生の有無及び／又は気泡発生量の検知は、例えば、前記連続画像数値情報が予め定めてある数値範囲から変動することを制御手段が把握することにより行うようにできる。   Here, the presence / absence of bubble generation on the reaction liquid surface and / or detection of the bubble generation amount due to fluctuations in the continuous image numerical information obtained by quantifying the continuous image information obtained by continuously photographing with the CCD camera is, for example, It can be performed by the control means grasping that the continuous image numerical information fluctuates from a predetermined numerical range.

例えば、所定の撮像箇所（例えば、反応容器内の反応液面より所定の高さで上方の反応容器の内壁面）における反応の開始後（すなわち、気泡が発生している状態）に把握した画像情報を数値化した数値が、当該撮像箇所における反応の開始前（すなわち、まだ気泡が発生していない状態）に把握した画像情報を数値化した数値から、予め定められている大きさ（数値）変動した段階で気泡が発生したと認識し、更に、所定の大きさ（数値）で変動した段階で、気泡発生量が所定のレベルに達したと認識するようにできる。   For example, an image grasped after the start of a reaction at a predetermined imaging location (for example, the inner wall surface of the reaction container at a predetermined height above the reaction liquid level in the reaction container) (that is, a state where bubbles are generated) The numerical value obtained by quantifying the information is a predetermined size (numerical value) from the numerical value obtained by quantifying the image information grasped before the start of the reaction at the imaging location (that is, in a state where bubbles are not yet generated). It is possible to recognize that bubbles have been generated at the stage of fluctuation, and to recognize that the amount of generated bubbles has reached a predetermined level at the stage of fluctuation at a predetermined size (numerical value).

例えば、培養器（反応容器）の内壁面を撮影した際の画像情報に含まれるＨ（色相）、Ｓ（彩度）、Ｖ（明度）をそれぞれ数値化し、これを制御手段に記憶させておく。なお、ＨＳＶ表色系での数値化は、Ｈ（色相）、Ｓ（彩度）、Ｖ（明度）について、それぞれ、０〜２５５の範囲で数値化される。   For example, H (hue), S (saturation), and V (brightness) included in the image information obtained when the inner wall surface of the incubator (reaction vessel) is photographed are each digitized and stored in the control means. . The numerical value in the HSV color system is expressed in the range of 0 to 255 for H (hue), S (saturation), and V (lightness).

そして、反応工程の開始後、気泡が発生した状態で撮像した画像情報に含まれるＨ（色相）、Ｓ（彩度）、Ｖ（明度）をそれぞれ数値化し、Ｈ（色相）、Ｓ（彩度）、Ｖ（明度）の中の少なくとも一種の数値が反応の開始前の数値から予め定められている数値以上に変動した際に、培養液面での気泡の発生の有無や 実際の発生量を、非人為的に検知するものである。   Then, after the start of the reaction process, H (hue), S (saturation), and V (lightness) included in the image information captured in the state where bubbles are generated are digitized, and H (hue) and S (saturation) are obtained. ) When at least one of the values in V (brightness) fluctuates from a value before the start of the reaction to a value greater than a predetermined value, the presence or absence of bubbles on the culture surface and the actual amount generated , Non-artificial detection.

すなわち、予め設定した、反応容器内の反応液面より所定の高さで上方の反応容器の内壁面、あるいは、反応容器内の反応液面より所定の高さで上方の攪拌軸を撮影していて得られるＨ（色相）、Ｓ（彩度）、Ｖ（明度）の中の少なくとも一種の情報から、培養液面での気泡の発生の有無や 実際の発生量を、非人為的に検知するものである。   That is, a predetermined inner wall surface of the reaction vessel at a predetermined height above the reaction liquid level in the reaction vessel or a stirring shaft above the reaction liquid surface in the reaction vessel at a predetermined height is imaged. The presence or absence of bubbles on the culture surface and the actual amount generated are detected artificially from at least one type of information in H (hue), S (saturation), and V (lightness) Is.

なお、画像情報を数値化する場合、例えば、ＨＳＶ表色系で数値化する場合、それらの数値は、周囲（周辺環境）の照明の色調・明るさや、培地（培養液）自体・気泡自体の色調などに影響されて変化する（依存する）可能性がある。そこで、前述したように、測定箇所における気泡発生前の画像情報から得られた数値、例えば、Ｈ（色相）、Ｓ（彩度）、Ｖ（明度）情報（数値）に対して、反応の開始後、どの程度の数値変動によって気泡発生と認め、どの程度の数値変動がどの程度の気泡発生量に相当するか、予め検討して検知数値を設定しておくことが望ましい。   In addition, when quantifying image information, for example, when quantifying in the HSV color system, those values are based on the color tone / brightness of the surrounding (surrounding environment) illumination, the culture medium (culture solution) itself, and the bubble itself. There is a possibility of changing (depending on) depending on the color tone. Therefore, as described above, the start of reaction with respect to numerical values obtained from image information before bubble generation at the measurement location, for example, H (hue), S (saturation), and V (lightness) information (numerical values). After that, it is desirable to set in advance a detection value by considering in advance how much numerical fluctuation it is recognized that bubbles are generated and how much numerical fluctuation corresponds to what amount of bubble generation.

本発明が提案する消泡装置は、前述した本発明による反応液の気泡検知方法の実施に供され、更に、この方法を利用して消泡処理を行うものである。   The defoaming apparatus proposed by the present invention is used in the above-described method for detecting bubbles in a reaction liquid according to the present invention, and further performs defoaming using this method.

この本発明が提案する消泡装置は、反応工程で気泡を発生させる反応液を収容している反応容器と、前記反応容器内の前記反応液に消泡剤を添加する消泡剤添加手段と、撮像手段と、制御手段とを備えている。   The defoaming device proposed by the present invention includes a reaction vessel that contains a reaction solution that generates bubbles in a reaction step, and an antifoaming agent addition unit that adds an antifoaming agent to the reaction solution in the reaction vessel. The imaging means and the control means are provided.

撮像手段は、前記反応容器内の反応液面上に近接する位置の前記反応容器の構造物を前記反応容器の外から前記反応容器のサイトグラスを介して連続的に撮影するもので、例えば、ＣＣＤカメラとすることができる。   The imaging means continuously images the structure of the reaction container at a position close to the reaction liquid surface in the reaction container from the outside of the reaction container through the sight glass of the reaction container, for example, It can be a CCD camera.

制御手段は、前記撮像手段から出力される画像情報の入力を受けて所定の処理を行うもので、例えば、コンピューターなどからなる。すなわち、制御手段は、前記撮像手段で連続的に撮影して得た連続画像情報を数値化した連続画像数値情報の変動により、前記消泡剤添加手段による前記反応容器内への消泡剤の添加の開始及び添加の中止を制御する。   The control means receives the input of the image information output from the imaging means and performs a predetermined process, and is composed of, for example, a computer. That is, the control means, by the fluctuation of the continuous image numerical information obtained by digitizing the continuous image information obtained by continuous imaging by the imaging means, the defoamer into the reaction container by the defoamer addition means Control the start and stop of addition.

すなわち、本発明の消泡装置は、前述した本発明の方法で検知した反応液面での気泡の発生の有無や実際の発生量に関する制御装置（コンピューター）の情報（判定）に基づいて、消泡剤添加手段、例えば、消泡剤添加用ポンプの運転（Ｏｎ）と停止（Ｏｆｆ）を制御し、消泡剤の添加の時期や実際の添加量を、機械的に自動化して的確に制御する。   That is, the defoaming device of the present invention is based on the information (determination) of the control device (computer) regarding the presence or absence of bubbles on the reaction liquid surface detected by the method of the present invention described above and the actual generation amount. Control the operation (On) and stop (Off) of the foaming agent addition means, for example, the antifoaming agent addition pump, and mechanically automate and accurately control the timing and actual addition amount of the antifoaming agent. To do.

例えば、コンピューターが取得したＣＣＤカメラからの画像情報で、画像情報を数値化した数値、例えば、画像情報に含まれるＨ（色相）、Ｓ（彩度）、Ｖ（明度）をそれぞれ数値化した数値が所定の大きさ（数値）で変動したと判定した際に、制御手段によって、消泡剤添加用ポンプが自動的に稼働開始し、反応液中へ消泡剤が自動的に添加される。   For example, numerical values obtained by digitizing image information, for example, numerical values obtained by digitizing H (hue), S (saturation), and V (brightness) included in the image information with image information from a CCD camera acquired by a computer. Is determined to have fluctuated by a predetermined size (numerical value), the control means automatically starts operation of the antifoaming agent addition pump, and the antifoaming agent is automatically added to the reaction solution.

これにより、反応液面（上面）に大量の気泡が発生して、反応液（気泡）が反応容器器外に溢れ出ることを防止して、連続的な長時間の反応工程を安定化できる。   Thus, a large amount of bubbles are generated on the reaction liquid surface (upper surface), and the reaction liquid (bubbles) is prevented from overflowing out of the reaction vessel, so that a continuous long-time reaction process can be stabilized.

一方、反応液中へ消泡剤が必要なだけ添加されて、気泡が十分に消滅すると、画像情報を数値化した数値、例えば、画像情報に含まれるＨ（色相）、Ｓ（彩度）、Ｖ（明度）をそれぞれ数値化した数値が所定の大きさ（数値）に戻ったと判定し、制御手段によって、消泡剤添加用ポンプの稼働が停止させられる。   On the other hand, when the necessary amount of antifoaming agent is added to the reaction solution and the bubbles are sufficiently eliminated, numerical values obtained by quantifying the image information, for example, H (hue), S (saturation) included in the image information, It is determined that the numerical values obtained by quantifying V (lightness) have returned to a predetermined size (numerical value), and the operation of the antifoaming agent addition pump is stopped by the control means.

本発明の消泡装置が以上の操作（制御）を繰り返すことで、反応工程で気泡が生成される化学反応、例えば、好気性培養による連続的な長時間の発酵工程などを、非人為的に安定して適切に維持することができる。   The anti-foaming device of the present invention repeats the above operation (control), whereby a chemical reaction in which bubbles are generated in the reaction process, for example, a continuous long-time fermentation process by aerobic culture, etc. It can be maintained stably and properly.

このように、本発明によれば、反応工程で気泡が生成される化学反応、例えば、好気性培養による連続的な長時間の発酵工程などにおいて、反応容器内の反応液面上に近接する位置の反応容器の構造物（例えば、反応容器内の反応液面と、内壁面との境界部分）を、反応容器外からサイトグラス（のぞき窓）を通してＣＣＤカメラで連続的に撮影し、その画像情報をコンピューターで処理（モニター）することで、反応液面での気泡の発生の有無や実際の発生量を、機械的に自動化して正確に検知できる。   Thus, according to the present invention, in a chemical reaction in which bubbles are generated in the reaction process, such as a continuous long-time fermentation process by aerobic culture, the position close to the reaction liquid surface in the reaction vessel The structure of the reaction vessel (for example, the boundary between the reaction liquid level in the reaction vessel and the inner wall surface) is continuously photographed from outside the reaction vessel through a sight glass (view window) with a CCD camera, and the image information By processing (monitoring) with a computer, the presence or absence of bubbles on the surface of the reaction solution and the actual amount generated can be detected automatically and accurately.

更に、前記本発明の方法で検知した反応液面での気泡の発生の有無や実際の発生量に関するコンピューターの情報（判定）に基づいて、消泡剤添加用ポンプの運転（Ｏｎ）と停止（Ｏｆｆ）を制御しながら、消泡剤の添加の時期や実際の添加量を、機械的に自動化して的確に制御できる。   Furthermore, based on the information (determination) of the presence or absence of bubbles on the reaction liquid surface detected by the method of the present invention and the information (determination) of the actual generation amount, the operation (On) and stop ( While controlling (Off), the timing of addition of the antifoaming agent and the actual amount added can be mechanically automated and accurately controlled.

つまり、本発明の消泡装置によれば、撮像装置（ＣＣＤカメラ）を解して制御手段（コンピューター）が把握した画像情報の分析と、消泡剤添加用ポンプの稼働とは連動しており、コンピューターの制御系により、消泡剤添加用ポンプの運転と停止を制御する。コンピューターで気泡の発生を判定すると、消泡剤添加用ポンプが自動的に稼働し、反応液中へ消泡剤が自動的に添加される。一方、反応液中へ消泡剤が必要なだけ添加されて、気泡の消滅を判定すると、消泡剤添加用ポンプの稼働を停止する。この操作により、反応工程で気泡が生成される化学反応、例えば、好気性培養による連続的な長時間の発酵工程などを非人為的に安定して適切に維持できる。   That is, according to the antifoaming device of the present invention, the analysis of the image information grasped by the control means (computer) through the imaging device (CCD camera) and the operation of the antifoaming agent addition pump are linked. The operation and stop of the antifoam addition pump are controlled by a computer control system. When the generation of bubbles is judged by the computer, the antifoaming agent adding pump is automatically operated, and the antifoaming agent is automatically added to the reaction solution. On the other hand, when the necessary amount of antifoaming agent is added to the reaction solution and the disappearance of the bubbles is determined, the operation of the antifoaming agent addition pump is stopped. By this operation, a chemical reaction in which bubbles are generated in the reaction process, for example, a continuous long-time fermentation process by aerobic culture can be stably and appropriately maintained artificially.

本発明によれば、反応容器内の状態を反応容器外から測定（検知）するため、センサーが反応液や気泡と物理的に非接触になる。   According to the present invention, since the state in the reaction container is measured (detected) from outside the reaction container, the sensor is not physically in contact with the reaction liquid or bubbles.

例えば、培養（発酵）のように衛生的で無菌的操作が要求されるような化学反応工程に、従来の接触式のセンサーを用いる方法・装置が採用された場合、実際に消泡した後に、気泡の成分や培養菌体などが センサーに付着して残存し、センサーが誤作動を起こす可能性があった。しかし、本発明によれば、センサーが反応液や気泡と物理的に非接触になるので、衛生的で培養（発酵）のような無菌的操作に適しており、培養液や気泡の成分の接触などにより、センサーが誤作動を起こすことがない。   For example, when a conventional method or device using a contact-type sensor is employed in a chemical reaction process that requires hygienic and aseptic operation such as culture (fermentation), after actually defoaming, Bubble components and cultured cells remained on the sensor and could cause the sensor to malfunction. However, according to the present invention, the sensor is physically non-contact with the reaction solution and bubbles, and thus is suitable for hygienic and aseptic operation such as culture (fermentation). For example, the sensor will not malfunction.

本発明によれば、反応容器内の状態を反応容器外から測定（検知）するため、反応容器内に特別な設備（構造物）を必要としない。そこで、反応容器内の滅菌性や無菌性が向上する。   According to the present invention, since the state in the reaction vessel is measured (detected) from outside the reaction vessel, no special equipment (structure) is required in the reaction vessel. Therefore, sterility and sterility in the reaction container are improved.

例えば、反応容器内に接触式のセンサーなどの設備が存在すると、反応容器内の滅菌時に蒸気などが十分に行き渡らず、滅菌不良の箇所が生じる可能性があるが、本発明によれば、反応容器内に特別な設備（構造物）を必要としないため、このような不都合の発生を未然に防止できる。   For example, if there is equipment such as a contact-type sensor in the reaction container, steam or the like may not be sufficiently distributed during sterilization in the reaction container, and there may be a point of poor sterilization. Since no special equipment (structure) is required in the container, such inconvenience can be prevented in advance.

本発明によれば、反応容器内の状態を反応容器外から測定（検知）するため、反応容器内に特別な設備（構造物）を必要としない。そこで、反応容器内の洗浄性や保守性が向上する。   According to the present invention, since the state in the reaction vessel is measured (detected) from outside the reaction vessel, no special equipment (structure) is required in the reaction vessel. Therefore, the cleanability and maintainability in the reaction vessel are improved.

これに対して、例えば、反応容器内に接触式のセンサーなどの設備が存在する場合であって、反応容器内の定置洗浄（ＣＩＰ）を行うときには、洗浄剤や濯ぎ水などが十分に行き渡らず、洗浄不良の箇所が生じる可能性がある。この洗浄不良を防止するために、定置洗浄の開始前にセンサーなどを反応容器から取り外して、そのセンサーのみを手洗いするなどで作業性が低下する。本発明によれば、反応容器内に特別な設備（構造物）を必要としないので、反応容器内の洗浄性や保守性が向上する。   On the other hand, for example, when a contact-type sensor or the like is present in the reaction vessel, and when performing cleaning in place (CIP) in the reaction vessel, the cleaning agent or rinsing water is not sufficiently distributed. There is a possibility that a poorly cleaned part may occur. In order to prevent this cleaning failure, workability is lowered by removing a sensor or the like from the reaction container before starting the stationary cleaning and washing only the sensor by hand. According to the present invention, since no special equipment (structure) is required in the reaction vessel, the cleanability and maintainability in the reaction vessel are improved.

本発明によれば、サイトグラスが付属された反応容器で、反応容器内の状態を反応容器外から観察できれば、撮像手段（例えば、ＣＣＤカメラ）で撮影できるため、サイトグラスが付属されている、あらゆる反応容器に後付けで使用できる。   According to the present invention, in a reaction vessel attached with a sight glass, if the state inside the reaction vessel can be observed from the outside of the reaction vessel, it can be taken with an imaging means (for example, a CCD camera). Can be retrofitted to any reaction vessel.

これに対して、例えば、接触式のセンサーを用いる場合、反応容器の上面部に、そのセンサーを設置するための開口部が必要である。   On the other hand, for example, when a contact-type sensor is used, an opening for installing the sensor is required on the upper surface of the reaction vessel.

本発明によれば、反応容器の寸法（容量）などに影響されにくいため、あらゆる反応容器で後付けできる。   According to the present invention, since it is hardly affected by the dimensions (capacity) of the reaction vessel, it can be retrofitted in any reaction vessel.

これに対して、例えば、接触式のセンサーを使用する場合には、一般的に反応容器の容量が大きくなると、そのヘッドスペースも大きくなるため、長尺のセンサーを設置しなければならず、費用・滅菌性・洗浄性・作業性などで問題（トラブル）が発生しやすくなる。   On the other hand, for example, when using a contact-type sensor, generally, when the capacity of the reaction vessel increases, the head space also increases. -Problems (troubles) are likely to occur due to sterilization, cleaning, and workability.

以下、本発明に関して実施例を挙げて説明するが、本発明は、これにより限定されるものではない。   Hereinafter, although an example is given and explained about the present invention, the present invention is not limited by this.

図１を参照して本発明による反応液の気泡検知方法の実施に使用される本発明の消泡装置の一例を説明する。   With reference to FIG. 1, an example of the defoaming apparatus of the present invention used for carrying out the method for detecting bubbles in a reaction liquid according to the present invention will be described.

本発明の消泡装置は、サイトグラス６を備えている反応容器５、消泡剤添加手段を構成する消泡剤用タンク４と消泡剤用ポンプ３、撮像手段であるＣＣＤカメラ２、コンピューターからなる制御手段１を備えている。   The defoaming apparatus of the present invention includes a reaction vessel 5 equipped with a sight glass 6, a defoaming agent tank 4 and an antifoaming agent pump 3 constituting defoaming agent adding means, a CCD camera 2 as an imaging means, a computer. The control means 1 which consists of these is provided.

反応容器５には反応工程で気泡を発生させる反応液が収容される。反応工程では必要に応じて撹拌機７が作動され、反応容器１内に収容されている反応液が攪拌羽根８によって攪拌される。   The reaction vessel 5 contains a reaction solution that generates bubbles in the reaction process. In the reaction step, the stirrer 7 is operated as necessary, and the reaction liquid stored in the reaction vessel 1 is stirred by the stirring blade 8.

反応容器５に必要な反応液を投入し、また、スパージャー９から所定の反応原料の投入や、空気や酸素の通気（バブリング）を行い、反応液が所定の反応温度に維持されるように反応容器５を加温し、適宜、撹拌機７を作動させて攪拌を加え、反応容器５内で所定の化学反応を行わせる。   Necessary reaction liquid is charged into the reaction vessel 5 and predetermined reaction raw materials are charged from the sparger 9 and air or oxygen is bubbled so that the reaction liquid is maintained at the predetermined reaction temperature. The reaction vessel 5 is heated, and the stirrer 7 is appropriately operated to add stirring, and a predetermined chemical reaction is performed in the reaction vessel 5.

図示のように反応容器５の外に設置されているＣＣＤカメラ２がサイトグラス６を介して、反応容器５内の反応液面上に近接する位置の反応容器１の構造物を撮影する。   As shown in the figure, the CCD camera 2 installed outside the reaction vessel 5 photographs the structure of the reaction vessel 1 at a position close to the reaction liquid surface in the reaction vessel 5 through the sight glass 6.

図示の実施形態では、反応容器５内の反応液面よりの若干上側の反応容器５内壁面をＣＣＤカメラ２により撮影するようにしている。   In the illustrated embodiment, the inner wall surface of the reaction container 5 slightly above the reaction liquid surface in the reaction container 5 is photographed by the CCD camera 2.

コンピューターからなる制御手段１は、ＣＣＤカメラ２から出力される画像情報の入力を受けて所定の処理を行う。   The control means 1 composed of a computer performs predetermined processing upon receiving image information output from the CCD camera 2.

すなわち、制御手段１は、ＣＣＤカメラ２で連続的に撮影して得た連続画像情報を数値化した連続画像数値情報の変動により、消泡剤用タンク４及び消泡剤用ポンプ３による反応容器内への消泡剤の添加の開始及び添加の中止を制御している。   In other words, the control means 1 uses the defoaming agent tank 4 and the defoaming agent pump 3 to react with each other according to the fluctuation of the continuous image numerical information obtained by digitizing the continuous image information obtained by continuously photographing with the CCD camera 2. The start of addition of the antifoaming agent and the stop of the addition are controlled.

以下、反応容器５内で冬虫夏草菌糸体を好気培養した場合について、本発明による反応液の気泡検知方法及び、本発明の消泡装置の動作の一例を説明する。   Hereinafter, an example of the reaction liquid bubble detection method according to the present invention and the operation of the defoaming apparatus according to the present invention will be described in the case where the cordyceps mycelium is aerobically cultured in the reaction vessel 5.

冬虫夏草菌糸体の培養用に調製した１５００ｋｇの培養液を滅菌してから培養用のタンクとなる反応容器５へ投入した。   After sterilizing 1500 kg of the culture solution prepared for cultivating Cordyceps mycelium, it was put into a reaction vessel 5 serving as a culture tank.

次いで、冬虫夏草菌糸体Cordycepes sinensis 8819株を無菌的に接種し、好気培養を行った。   Subsequently, Cordycepes sinensis 8819 strain was inoculated aseptically and aerobic culture was performed.

培養条件の概要は下記の通りとした。   The outline of the culture conditions was as follows.

温度：２５±１ ℃
時間：７０±１０ｈ
撹拌：４５〜５３Ｈｚ
溶存酸素濃度：３０〜５０％（空気や酸素を通気（バブリング）して制御した。）
ｐＨ：５．５±０．１（アンモニア水溶液を添加して制御した。）
使用した消泡剤：アワブレークＬ−０１（太陽化学社製）。 Temperature: 25 ± 1 ° C
Time: 70 ± 10h
Agitation: 45-53 Hz
Dissolved oxygen concentration: 30 to 50% (Controlled by bubbling air and oxygen)
pH: 5.5 ± 0.1 (controlled by adding ammonia aqueous solution)
Antifoam used: Our break L-01 (manufactured by Taiyo Kagaku Co.).

ＣＣＤカメラ２にはキーエンス社製のＣＶ−０３３を使用し、制御装置１にはキーエンス社製のＣＶ−３００（モニタ内蔵、カラータイプ画像センサ）を使用した。   A CV-033 manufactured by Keyence Corporation was used for the CCD camera 2, and a CV-300 (color type image sensor with a built-in monitor) manufactured by Keyence Corporation was used for the control device 1.

まず、反応が開始される前の反応容器５の内壁面をＣＣＤカメラ２で撮影し、ＣＣＤカメラ２で得た画像情報を制御手段１で数値化した数値を初期値の０に設定した。また、同様にして、ＣＣＤカメラ２で得た画像情報を数値化した数値が４００を越えた時点で、消泡剤用ポンプ３の作動を開始させ（Ｏｎ）、その後、同様にして、ＣＣＤカメラ２で得た画像情報を数値化した数値が３５０を下回った時点で、消泡剤用ポンプ３の作動を停止（Ｏｆｆ）させる制御が実行されるように制御手段１を設定した。   First, the inner wall surface of the reaction vessel 5 before the start of the reaction was photographed with the CCD camera 2, and the numerical value obtained by digitizing the image information obtained by the CCD camera 2 with the control means 1 was set to an initial value of zero. Similarly, when the numerical value obtained by digitizing the image information obtained by the CCD camera 2 exceeds 400, the operation of the antifoaming agent pump 3 is started (On), and thereafter the CCD camera is similarly operated. The control means 1 was set so that the control for stopping the operation of the antifoaming agent pump 3 was performed when the numerical value obtained by digitizing the image information obtained in 2 was less than 350.

冬虫夏草菌糸体Cordycepes sinensis 8819株を無菌的に接種し、前記の条件で培養を開始したところ、培養液の泡立ちに伴い、連続的にＣＣＤカメラ２で撮影している画像情報を数値化した数値が変動した。培養液の泡立ちが激しくなると、ＣＣＤカメラ２は反応容器５の内壁面ではなく泡自体を撮影することになるためである。   Cordycepes sinensis 8819 strain was aseptically inoculated and the culture was started under the above conditions. As a result of the bubbling of the culture solution, the numerical values obtained by continuously quantifying the image information taken with the CCD camera 2 were It fluctuated. This is because when the foaming of the culture solution becomes intense, the CCD camera 2 takes a picture of the foam itself, not the inner wall surface of the reaction vessel 5.

前記の実施例では、約１２時間経過したところで、連続的にＣＣＤカメラ２で撮影している画像情報を数値化した数値が４００を越えた。そこで、制御装置１の制御により、自動的に消泡剤用ポンプ３がＯｎされ、消泡剤用タンク４から消泡剤が反応容器５内に投入された。   In the above embodiment, when about 12 hours passed, the numerical value obtained by digitizing the image information continuously captured by the CCD camera 2 exceeded 400. Therefore, under the control of the control device 1, the antifoaming agent pump 3 was automatically turned on, and the antifoaming agent was put into the reaction vessel 5 from the antifoaming agent tank 4.

連続的にＣＣＤカメラ２で撮影している画像情報を数値化した数値は、消泡剤の投入の開始後から３〜５秒で３５０を下回り、消泡剤用ポンプ３がＯｆｆされて、反応容器５内への消泡剤の投入が停止された。   The numerical value obtained by digitizing the image information continuously photographed by the CCD camera 2 falls below 350 in 3 to 5 seconds after the start of the introduction of the antifoaming agent, and the antifoaming agent pump 3 is turned off to react. The introduction of the antifoaming agent into the container 5 was stopped.

その後、連続的にＣＣＤカメラ２で撮影している画像情報を数値化した数値は、７５分〜８０分程度で経過するごとに４００を越えたので、前記と同様にして、自動的に消泡剤用ポンプ３をＯｎ、Ｏｆｆし、消泡剤を反応容器５内に投入する動作を繰返して、約６７時間で培養を終了した。   After that, the numerical value obtained by digitizing the image information continuously photographed by the CCD camera 2 exceeds 400 every 75 to 80 minutes. The agent pump 3 was turned on and off, and the operation of charging the antifoaming agent into the reaction vessel 5 was repeated, and the culture was completed in about 67 hours.

このとき、実際に投入した消泡剤（アワブレークＬ−０１）が約３０ｋｇとなり、培養液の収量は約１５３０ｋｇとなった。   At this time, the defoaming agent (Awabreak L-01) actually added was about 30 kg, and the yield of the culture solution was about 1530 kg.

前記実施例では、培養中に発生した泡立ちは確実に検知された。そして、連続的にＣＣＤカメラ２で撮影している画像情報を数値化した数値が４００を越えた時点で、即時に消泡剤が添加され、前記数値が３５０を下回った時点で、消泡剤添加を中止する動作を繰返すたびに泡立ちは消滅し、反応容器５から培養液が溢れることなく、安定して連続培養を行うことができた。   In the example, foaming generated during the culture was reliably detected. Then, when the numerical value obtained by quantifying the image information continuously captured by the CCD camera 2 exceeds 400, the antifoaming agent is immediately added, and when the numerical value falls below 350, the antifoaming agent is added. Each time the operation for stopping the addition was repeated, the foaming disappeared, and the culture solution did not overflow from the reaction vessel 5 and stable continuous culture could be performed.

次に、前記と同様の条件で準備した１５００ｋｇの培養液及び、培養条件で、ＣＣＤカメラ２にキーエンス社製のＣＶ−０３５Ｃを使用し、制御装置１にはキーエンス社製のＣＶ−５０００（モニタ内蔵、カラータイプ画像センサ）を使用して同様に好気培養を行った。   Next, a 1500 kg culture solution prepared under the same conditions as described above, and a CV-035C manufactured by Keyence Co., Ltd. was used for the CCD camera 2 under the culture conditions. An aerobic culture was similarly performed using a built-in color type image sensor.

まず、反応が開始される前の反応容器５内壁面をＣＣＤカメラ２で撮影し、ＣＣＤカメラ２で得た画像情報に含まれるＨ（色相）を制御手段１で数値化したところ、６０．１４１であった。   First, the inner wall surface of the reaction vessel 5 before the start of the reaction was photographed by the CCD camera 2 and H (hue) included in the image information obtained by the CCD camera 2 was quantified by the control means 1. Met.

ＣＣＤカメラ２で得た画像情報に含まれるＨ（色相）を制御手段１で数値化した数値が２６を下回った時点で、消泡剤用ポンプ３の作動を開始させ（Ｏｎ）、その後、同様にして、ＣＣＤカメラ２で得た画像情報に含まれるＨ（色相）を制御手段１で数値化した数値が３５を上回った時点で、消泡剤用ポンプ３の作動を停止（Ｏｆｆ）させる制御が実行されるように制御手段１を設定した。   When the numerical value obtained by digitizing H (hue) contained in the image information obtained by the CCD camera 2 by the control means 1 is less than 26, the operation of the antifoaming agent pump 3 is started (On). Then, when the numerical value obtained by digitizing H (hue) included in the image information obtained by the CCD camera 2 by the control means 1 exceeds 35, the operation of stopping the operation of the antifoaming agent pump 3 is turned off. The control means 1 is set so that is executed.

この場合にも、約１２時間経過したところで、連続的にＣＣＤカメラ２で撮影している画像情報に含まれるＨ（色相）を制御手段１で数値化した数値が２６を下回った（２５．１２３）。そこで、制御装置１の制御により、自動的に消泡剤用ポンプ３がＯｎされ、消泡剤用タンク４から消泡剤が反応容器５内に投入された。   Also in this case, when about 12 hours have passed, the numerical value obtained by quantifying H (hue) included in the image information continuously captured by the CCD camera 2 by the control means 1 is less than 26 (25.123). ). Therefore, under the control of the control device 1, the antifoaming agent pump 3 was automatically turned on, and the antifoaming agent was put into the reaction vessel 5 from the antifoaming agent tank 4.

連続的にＣＣＤカメラ２で撮影している画像情報に含まれるＨ（色相）を制御手段１で数値化した数値は、消泡剤の投入の開始後から３〜５秒で３５を上回り（３５．６９８）、消泡剤用ポンプ３がＯｆｆされて、反応容器５内への消泡剤の投入が停止された。   The numerical value obtained by digitizing H (hue) included in the image information continuously photographed by the CCD camera 2 by the control means 1 exceeds 35 in 3 to 5 seconds after starting the introduction of the antifoaming agent (35 698), the defoamer pump 3 was turned off, and the introduction of the defoamer into the reaction vessel 5 was stopped.

その後、連続的にＣＣＤカメラ２で撮影している画像情報に含まれるＨ（色相）を制御手段１で数値化した数値は、７５分〜８０分程度が経過するごとに２６を下回り、前記と同様にして、自動的に消泡剤用ポンプ３をＯｎ、Ｏｆｆし、消泡剤を反応容器５内に投入する動作を繰返して、約６７時間で培養を終了した。   Thereafter, H (hue) included in the image information continuously photographed by the CCD camera 2 is digitized by the control means 1 and falls below 26 every 75 to 80 minutes. Similarly, the operation of automatically turning on and off the antifoam pump 3 and feeding the antifoam agent into the reaction vessel 5 was repeated, and the culture was completed in about 67 hours.

このとき、実際に投入した消泡剤（アワブレークＬ−０１）が約３０ｋｇとなり、培養液の収量は約１５３０ｋｇとなった。   At this time, the defoaming agent (Awabreak L-01) actually added was about 30 kg, and the yield of the culture solution was about 1530 kg.

この実施例でも、培養中に発生した泡立ちは確実に検知された。そして、連続的にＣＣＤカメラ２で撮影している画像情報に含まれるＨ（色相）を制御手段１で数値化した数値が２６を下回った時点で、即時に消泡剤が添加され、前記数値が３５を上回った時点で、消泡剤添加を中止する動作を繰返すたびに泡立ちは消滅し、反応容器５から培養液が溢れることなく、安定して連続培養を行うことができた。   Also in this example, foaming generated during the culture was reliably detected. Then, when the numerical value obtained by quantifying H (hue) included in the image information continuously photographed by the CCD camera 2 is less than 26, the antifoaming agent is immediately added, and the numerical value When the value exceeded 35, the foaming disappeared each time the operation of stopping the addition of the antifoaming agent was repeated, and the culture solution did not overflow from the reaction vessel 5 and stable continuous culture could be performed.

一方、対照としてＣＣＤカメラ２、制御装置１を動作させない以外は前記実施例と同様の条件で培養を行ったところ、泡立ちが激しく、反応容器５から培養液が大量に溢れて、設備や室内を汚すと共に、培養液の３分の１程度が流失し、収量の著しい低下を引き起こした。   On the other hand, when the culture was performed under the same conditions as in the above example except that the CCD camera 2 and the control device 1 were not operated as a control, the foaming was intense and the culture solution overflowed from the reaction vessel 5 in large quantities, so Along with soiling, about one third of the culture broth was washed away, causing a significant decrease in yield.

１ 制御手段
２ ＣＣＤカメラ
３ 消泡剤用ポンプ
４ 消泡剤用タンク
５ 反応容器
６ サイトグラス
７ 撹拌機
８ 攪拌羽根
９ スパージャー DESCRIPTION OF SYMBOLS 1 Control means 2 CCD camera 3 Antifoam pump 4 Antifoam tank 5 Reaction container 6 Sight glass 7 Stirrer 8 Stirrer blade 9 Sparger

Claims (4)

反応工程で気泡を発生させる反応液を収容している反応容器内の反応液面と、前記反応容器の内壁面との間の境界部分であって前記反応液面より上側において前記反応液面に近接する位置の前記反応容器の前記内壁面、又は、反応液面と、前記反応液内に挿入されている撹拌軸との間の境界部分であって前記反応液面より上側において前記反応液面に近接する位置の前記撹拌軸を前記反応容器の外から前記反応容器のサイトグラスを介して連続的に撮影し、当該連続的に撮影して得た連続画像情報を数値化した連続画像数値情報の変動により、前記反応液表面での気泡発生の有無及び／又は気泡発生量を検知する反応液の気泡検知方法であって、
前記撮影している前記内壁面、又は、前記撹拌軸における反応開始前に把握した画像情報を数値化した数値から、反応開始後に把握した画像情報を数値化した数値が、予め定めてある数値範囲変動することにより、前記連続画像数値情報の変動を判定することを特徴とする反応液の気泡検知方法。 It is a boundary part between the reaction liquid surface in the reaction container containing the reaction liquid that generates bubbles in the reaction step and the inner wall surface of the reaction container, and is above the reaction liquid surface and on the reaction liquid surface . The inner wall surface of the reaction vessel at a close position or a boundary portion between the reaction liquid surface and the stirring shaft inserted into the reaction liquid, and the reaction liquid surface above the reaction liquid surface Continuous image numerical information obtained by continuously imaging the stirring shaft at a position close to the outside through the sight glass of the reaction container from the outside of the reaction container and digitizing the continuous image information obtained by the continuous imaging the variation, detect the presence and / or the bubble generation of the bubble generation in the reaction liquid surface a reaction solution of the bubble detection method,
A numerical value range in which a numerical value obtained by quantifying the image information obtained after the start of the reaction from a numerical value obtained by quantifying the image information obtained before the start of the reaction on the inner wall surface or the stirring shaft is set in advance. A method for detecting a bubble in a reaction liquid, wherein the change in the continuous image numerical information is determined by changing . 前記連続画像情報に含まれるＨ（色相）、Ｓ（彩度）、Ｖ（明度）をそれぞれ数値化した前記連続画像数値情報の中の少なくとも一種を用いて前記連続画像数値情報の変動を判定することを特徴とする請求項１記載の反応液の気泡検知方法。   The variation of the continuous image numerical information is determined using at least one of the continuous image numerical information obtained by digitizing H (hue), S (saturation), and V (lightness) included in the continuous image information. The method of detecting bubbles in a reaction liquid according to claim 1. 反応工程で気泡を発生させる反応液を収容している反応容器と、
前記反応容器内の前記反応液に消泡剤を添加する消泡剤添加手段と、
前記反応容器内の反応液面と、前記反応容器の内壁面との間の境界部分であって前記反応液面より上側において前記反応液面に近接する位置の前記反応容器の内壁面、又は、反応液面と、前記反応液内に挿入されている撹拌軸との間の境界部分であって前記反応液面より上側において前記反応液面に近接する位置の前記撹拌軸を前記反応容器の外から前記反応容器のサイトグラスを介して連続的に撮影する撮像手段と、
前記撮像手段で連続的に撮影して得た連続画像情報を数値化した連続画像数値情報の変動により、前記反応液表面での気泡発生の有無及び／又は気泡発生量を検知し、前記消泡剤添加手段による前記反応容器内への消泡剤の添加開始及び添加中止を制御する制御手段と
を備えている消泡装置であって、
前記制御装置は、前記撮影している前記内壁面、又は、前記撹拌軸における反応開始前に把握した画像情報を数値化した数値から、反応開始後に把握した画像情報を数値化した数値が、予め定めてある数値範囲変動することにより、前記連続画像数値情報の変動を判定する
ことを特徴とする消泡装置。 A reaction vessel containing a reaction solution that generates bubbles in the reaction process;
An antifoaming agent adding means for adding an antifoaming agent to the reaction solution in the reaction vessel;
The inner wall surface of the reaction vessel at a position near the reaction liquid surface above the reaction liquid surface, which is a boundary portion between the reaction liquid surface in the reaction vessel and the inner wall surface of the reaction vessel, or The stirring shaft at a position close to the reaction liquid surface at a boundary portion between the reaction liquid surface and the stirring shaft inserted into the reaction liquid and above the reaction liquid surface is disposed outside the reaction vessel. Imaging means for continuously photographing through the sight glass of the reaction vessel,
The presence / absence of bubbles on the reaction liquid surface and / or the amount of bubbles generated is detected based on fluctuations in the continuous image numerical information obtained by digitizing the continuous image information obtained by continuously photographing with the imaging means, and the defoaming is performed. Control means for controlling the start and stop of the addition of the antifoaming agent into the reaction vessel by the agent addition means;
A defoaming device comprising:
From the numerical value obtained by quantifying the image information obtained before the start of the reaction on the inner wall surface or the stirring shaft, the control device is configured in advance to obtain a numerical value obtained by quantifying the image information obtained after the start of the reaction. The variation of the numerical value information of the continuous image is determined by changing the predetermined numerical range.
A defoaming device characterized by that . 前記制御装置は、前記連続画像情報に含まれるＨ（色相）、Ｓ（彩度）、Ｖ（明度）をそれぞれ数値化した前記連続画像数値情報の中の少なくとも一種を用いて、前記連続画像数値情報の変動を判定することを特徴とする請求項３記載の消泡装置。 The control device uses the continuous image numerical value by using at least one of the continuous image numerical information obtained by digitizing H (hue), S (saturation), and V (brightness) included in the continuous image information. The defoaming apparatus according to claim 3, wherein a change in information is determined .
JP2009069053A 2009-03-19 2009-03-19 Bubble detection method and defoaming device for reaction liquid Active JP5500618B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2009069053A JP5500618B2 (en) 2009-03-19 2009-03-19 Bubble detection method and defoaming device for reaction liquid

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2009069053A JP5500618B2 (en) 2009-03-19 2009-03-19 Bubble detection method and defoaming device for reaction liquid

Publications (2)

Publication Number Publication Date
JP2010220499A JP2010220499A (en) 2010-10-07
JP5500618B2 true JP5500618B2 (en) 2014-05-21

Family

ID=43038395

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2009069053A Active JP5500618B2 (en) 2009-03-19 2009-03-19 Bubble detection method and defoaming device for reaction liquid

Country Status (1)

Country Link
JP (1) JP5500618B2 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201614717D0 (en) * 2016-08-31 2016-10-12 Ge Healthcare Bio Sciences Ab Detection of foam levels
SG11202105998PA (en) * 2019-03-28 2021-07-29 Emd Millipore Corp Use of vision systems in biomanufacturing processes
KR102460080B1 (en) * 2020-07-31 2022-10-28 한국과학기술정보연구원 Apparatus for detecting a bubble and method thereof
EP3957712A1 (en) * 2020-08-21 2022-02-23 Sartorius Stedim Data Analytics AB Automated foam detection
BR112023023070A2 (en) * 2021-05-06 2024-01-30 Ajinomoto Kk APPARATUS AND METHOD FOR CONTROLLING FERMENTATION, AND METHOD FOR MANUFACTURING AN OBJECTIVE SUBSTANCE BY FERMENTATION

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR910004113B1 (en) * 1988-12-30 1991-06-22 삼성전자 주식회사 Inspection instrument for the formentation condition of vegetables
JPH0424498U (en) * 1990-06-20 1992-02-27
JP3116103B2 (en) * 1991-11-22 2000-12-11 味の素株式会社 Culture device and defoaming control method in fermentation production by aerobic culture
JP3018178B1 (en) * 1998-11-02 2000-03-13 工業技術院長 Method and apparatus for measuring bubbles using optical fiber probe
JP2004061333A (en) * 2002-07-30 2004-02-26 Tokyo Micro Device Kk Foaming degree inspection device for test liquid for medical use
JP2004114181A (en) * 2002-09-24 2004-04-15 Okuma Corp Defoaming agent supplying device
JP2007222805A (en) * 2006-02-24 2007-09-06 Mitsubishi Chemical Engineering Corp Fine air bubble forming apparatus
JP2007322324A (en) * 2006-06-02 2007-12-13 Olympus Corp Analyzer

Also Published As

Publication number Publication date
JP2010220499A (en) 2010-10-07

Similar Documents

Publication Publication Date Title
JP5500618B2 (en) Bubble detection method and defoaming device for reaction liquid
JP5285666B2 (en) Cell culture equipment
JP5332610B2 (en) Cell detachment determination apparatus, cell detachment determination method, and cell culture apparatus
EP2489638B1 (en) Apparatus for reducing waste lithographic printing plate developing liquid
TW354340B (en) Apparatus and process for cleaning soiled garments and fabrics by removing soiling substances therefrom
WO2018038214A1 (en) Cell culture system, culture unit, automatic cell culture device, and cell culture device for transport
CN208617835U (en) A kind of de-bubble fermentor
JP6726696B2 (en) Diluted sludge imaging system, flocculant addition amount control system, sludge concentration system, diluted sludge imaging method
JP2006014693A (en) Cell culture system and method for cell culture
JP2013188678A (en) Drainage treatment system
JP4908016B2 (en) Waste water treatment control system and control method
US11441115B2 (en) Cell culture device
JP2004016861A (en) Steam heating method
CN205774654U (en) A kind of VD Monitor controller used in furnace
JP5105795B2 (en) Membrane separation tank and operation method
KR20100094742A (en) Apparatus and method for dissolving gas with high efficiency
CN220195741U (en) Pickling device for activated carbon production
US9993144B2 (en) Control method for endoscope reprocessor
JP6944282B2 (en) Methane fermentation system and monitoring method for methanogens
CN110595809B (en) Test system for medical cleaning machine and use method thereof
WO2023032269A1 (en) Pretreatment device and pretreatment method
JP2024063798A (en) Imaging device, water treatment system and air supply device
KR19980015168A (en) Deodorizing water exchanger and method of food garbage disposal machine
WO2019245078A1 (en) Stem cell proliferation device
JP6530266B2 (en) Intake and exhaust control method, intake and exhaust control mechanism and surge tank

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20111007

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20130820

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20131018

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20140304

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20140306

R150 Certificate of patent or registration of utility model

Ref document number: 5500618

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

S531 Written request for registration of change of domicile

Free format text: JAPANESE INTERMEDIATE CODE: R313531

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250