EP2084260A1 - Method and device for aeration, particularly for microbiological fermentation and for cell cultivation - Google Patents
Method and device for aeration, particularly for microbiological fermentation and for cell cultivationInfo
- Publication number
- EP2084260A1 EP2084260A1 EP07819323A EP07819323A EP2084260A1 EP 2084260 A1 EP2084260 A1 EP 2084260A1 EP 07819323 A EP07819323 A EP 07819323A EP 07819323 A EP07819323 A EP 07819323A EP 2084260 A1 EP2084260 A1 EP 2084260A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- reactor
- gassing
- elements
- agitator shaft
- gas
- 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- Withdrawn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
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
- B01F27/80—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis
- B01F27/90—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with paddles or arms
- B01F27/902—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with paddles or arms cooperating with intermeshing elements fixed on the receptacle walls
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/20—Mixing gases with liquids
- B01F23/23—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids
- B01F23/233—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using driven stirrers with completely immersed stirring elements
- B01F23/2331—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using driven stirrers with completely immersed stirring elements characterised by the introduction of the gas along the axis of the stirrer or along the stirrer elements
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- 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/02—Stirrer or mobile mixing elements
- C12M27/04—Stirrer or mobile mixing elements with introduction of gas through the stirrer or mixing element
Definitions
- the invention relates to a method and a device for gassing, in particular for the microbiological fermentation and cultivation of cells in a closed space, according to the preamble of claim 1.
- a device of this type is known for example from EP-AO 365 621.
- a vertical agitator shaft is arranged with a number of superimposed in several levels Bega- sungs or stirring elements.
- the gassing elements and Preferably, the stirring elements are hollow, connected to gas supply channels and provided with at least one gas-permeable part.
- the agitator shaft protrudes with its one end through the reactor wall and is driven by an outside of the reactor arranged electric motor. For example, since a cell growing bioreactor must be hermetically sealed, the sealing of the rotating in the stationary reactor agitator or drive shaft is a real problem.
- the present invention has for its object to provide a method with an optimized gassing of a liquid in the reactor and to simplify a device of the type mentioned constructive and sterile technology to improve.
- the gassing elements are designed such that they can be made variable depending on the oxygen requirement of the product formers.
- the gas bubbles must be uniformly introduced as the smallest possible bubbles in the liquid. Due to the areal to be adapted ventilation slots these requirements are met.
- the inventive device is simple and inexpensive, since all sealing problems with respect to the rotating agitator shaft for Outside atmosphere omitted and a hermetically sealed reactor space can be ensured without much effort.
- the device can also be designed to save space, since no external drive is needed.
- gassing elements provided with inserts over the height of the reactor, which allow a metered gas supply.
- FIG. 1 schematically shows an apparatus according to the invention for gassing with gassing or stirring elements arranged one above the other in four planes;
- FIG. 2 shows a gassing element according to the invention according to FIG. 1 viewed from above;
- FIG. 3 shows a cross section through the gassing element according to FIG. 2;
- Fig. 4 shows an embodiment of an inventive Begasungsl. Stirring element in side view
- FIG. 5 the gassing or stirring element of FIG. 4 in plan view.
- FIG. 1 shows a reactor 1 which forms a bioreactor intended for microbiological fermentation and cultivation of cells.
- a stirrer shaft 2 is rotatably arranged, which is held with its one end in a shaft suspension or mounting 3 and supported with the other in a bottom bearing 4.
- the shaft suspension or storage 3 is assigned to a reactor cover Ia. - A -
- a plurality of radially extending aeration elements 15 or agitating elements 10 are arranged one above the other in several planes, in this case in three planes aeration elements 15 and in the two intermediate planes agitating elements 10.
- smart elements 17 are preferably provided on the inside of the reactor wall. which serve as a rotation prevention of the liquid and sometimes cause homogenization at low rotational speed of the agitator shaft 2.
- the gassing elements 15 are designed in such a way that they are kept variable depending on the oxygen requirement of the product formation occurring through the gassing and that such gassing of the liquid in the reactor causes the gases to be uniformly introduced into the liquid as microbubbles preferably be introduced with a diameter of less than one millimeter. In addition, a homogeneous distribution of the bubbles in the liquid column should take place.
- the gassing elements 15 each comprise an elongated hollow body with gas-permeable inserts 16 arranged approximately over the entire length on the lower and upper side.
- the hollow body forming a respective gassing element 15 with a corresponding gas supply channel 11 is tubular in this case , so that the gas to be injected is guided to the end of the hollow body.
- These gas-permeable inserts 16 are preferably made of a sintered metal, such as stainless steel. But they could also be made of ceramic or a plastic.
- these gassing elements 15 distributed over the height of the reactor 1 are provided with inserts 16, which are provided either with differently sized surfaces or with different porosities, depending in particular on the oxygen requirement of the product formers.
- the hydrostatic pressure of the liquid is taken into account.
- the gassing elements 15 therefore, larger surfaces or a larger porosity of the inserts 16 are to be provided in the lower region of the reactor 1 than in the upper region.
- the gassing elements 15 are supplied by a guided through the agitator shaft 2 gas supply channel 1 1, 12 with the gas.
- the stirring elements 10 projecting radially away from the agitator shaft 2 are arranged at different levels. In principle, they could also be equipped with inserts 16 and at the same time serve as gassing elements. With them, the stirring effect for homogenization of the reactor contents is ensured, with a low rotational speed (5 to 100 U / min) can be selected, since in the subject method, a dispersion of the gas bubbles is not necessary.
- a drive member 20 is provided with a wing portion 20a fixed at the end and a separate gas and / or air supply 21 with which this agitator shaft 2 is rotatable.
- This wing part 20a has at least one, optionally three recoil nozzles 22, which are directed in the circumferential direction of the agitator shaft 2 substantially.
- the wing part 20a provided with the recoil nozzles 20 is connected in each case via the separate gas supply channel 21 to a vertical gas supply channel 23 guided by the rotating agitator shaft 2, which in turn has a transfer unit 13 is in communication with a stationary in a reactor wall Ib installed gas supply line 24.
- gas may be introduced into the wing portion 20a from a pressurized gas source in such an amount and under such a pressure that the gas exiting the recoil nozzles 20 promotes propulsion of the entire agitator, i. all with the agitator shaft 2 rotatably connected stirring and / or gassing elements 10, 15 causes.
- the required amount of gas and the gas pressure as a pulse generator for the propulsion are achieved in the combination of the outside taking place Gasmengeregulleiter in coordination with a corresponding nozzle cross-section.
- the drive of the agitator shaft 2 provided with the stirring and / or gassing alone on the propulsion causing remindstossdüsen 20 done, and the agitator shaft 2 does not need through the reactor wall be led to an outside drive. It is located inside the reactor 1, held in the shaft suspension 3 and guided in the bottom bearing 4, for example a Teflon bearing.
- the bioreactor is hermetically sealed. The opening into the reactor 1 and installed in the reactor wall or in the reactor shell Ib stationary, preferably welded gas supply lines 14, 24 pose no risk of leakage.
- the agitator shaft 2 could be via a known magnetic coupling (instead of the bottom bearing 4) additionally from a lying outside of the reactor 1 engine be driven without having to protrude the reactor wall.
- the wing parts 10a advantageously have a fluid-technically optimized, aerodynamic shape, as indicated in FIGS. 4 and 5. This favors the rotational movement of the stirring elements 10th
- the same gas can be used for propulsion, which is also provided for gassing the fermentation broth, e.g. Sterile air, pure oxygen or an oxygen / nitrogen mixture.
- the device according to the invention for gassing, in particular for the microbiological fermentation and cultivation of cells in a closed space is simple and inexpensive, since all sealing problems with respect to the rotating agitator shaft are eliminated and a hermetically sealed reactor space can be ensured without much effort.
- the device can be designed to save space, since no external drive is needed.
- gassing or stirring elements can also be varied depending on the size of the reactor.
- the inserts in the gassing elements could also be oriented obliquely downwards or upwards or horizontally.
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- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Sustainable Development (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
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- Biomedical Technology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention relates to a method and a device for aeration, particularly for microbiological fermentation and for cell cultivation in a closed chamber. The invention comprises a sterilizable reactor (1) and a vertical stirring shaft (2) with numerous aeration and/or stirring elements (10) which are attached thereto and arranged in multiple levels vertically. The aeration elements (15) are constructed to create such an aeration of the liquid in the reactor that the gases are evenly introduced into the liquid as micro bubbles. The invention also comprises recoil nozzles (20) connected to gas feed channels (11, 12, 14) for the purpose of driving the aeration and/or stirring elements (10) attached to the rotatably mounted stirring shaft (2). The result is a space-saving and absolutely hermetic construction of such a device.
Description
Verfahren und Vorrichtung zum Begasen, insbesondere für die mikrobiologische Fermentation und Kultivierung von Zellen Method and device for gassing, in particular for the microbiological fermentation and cultivation of cells
Die Erfindung betrifft eine Verfahren sowie eine Vorrichtung zum Begasen, insbesondere für die mikrobiologische Fermentation und Kultivierung von Zellen in einem geschlossenen Raum, gemäss dem Oberbegriff des Anspruches 1.The invention relates to a method and a device for gassing, in particular for the microbiological fermentation and cultivation of cells in a closed space, according to the preamble of claim 1.
Eine Vorrichtung dieser Art ist beispielsweise aus der EP-A-O 365 621 bekannt. In einem sterilisierbaren Reaktor ist eine vertikale Rührerwelle mit einer Anzahl von in mehreren Ebenen übereinander angeordneten Bega- sungs- bzw. Rührelementen angeordnet. Die Begasungselemente und vor-
zugsweise auch die Rührelemente sind hohlförmig ausgebildet, an Gaszufuhrkanäle angeschlossen und mit mindestens einem gasdurchlässigen Teil versehen. Die Rührerwelle ragt mit ihrem einen Ende die Reaktorwand hindurch und wird von einem ausserhalb des Reaktors angeordneten Elektromotor angetrieben. Da beispielsweise ein Zellzucht-Bioreaktor hermetisch geschlossen sein muss, stellt die Abdichtung der im ortsfesten Reaktor rotierenden Rührer- bzw. Antriebswelle ein echtes Problem dar.A device of this type is known for example from EP-AO 365 621. In a sterilizable reactor, a vertical agitator shaft is arranged with a number of superimposed in several levels Bega- sungs or stirring elements. The gassing elements and Preferably, the stirring elements are hollow, connected to gas supply channels and provided with at least one gas-permeable part. The agitator shaft protrudes with its one end through the reactor wall and is driven by an outside of the reactor arranged electric motor. For example, since a cell growing bioreactor must be hermetically sealed, the sealing of the rotating in the stationary reactor agitator or drive shaft is a real problem.
Der vorliegenden Erfindung liegt die Aufgabe zugrunde, ein Verfahren mit einem optimierten Begasen einer Flüssigkeit im Reaktor zu erzielen sowie eine Vorrichtung der eingangs genannten Art konstruktiv zu vereinfachen und steriltechnisch zu verbessern.The present invention has for its object to provide a method with an optimized gassing of a liquid in the reactor and to simplify a device of the type mentioned constructive and sterile technology to improve.
Diese Aufgabe wird erfindungsgemäss durch ein Verfahren mit den Merkmalen nach Anspruch 1 sowie einer Vorrichtung gemäss den Merkmalen nach Anspruch 3 bzw. 5 gelöst.This object is achieved by a method with the features of claim 1 and a device according to the features of claim 3 and 5, respectively.
Weitere bevorzugte Ausgestaltungen des erfindungsgemässen Verfahrens bzw. der Vorrichtung bilden den Gegenstand der abhängigen Ansprüche.Further preferred embodiments of the method according to the invention and of the device form the subject of the dependent claims.
Bei dem erfindungsgemässen Verfahren sind die Begasungselemente derart ausgebildet, dass sie in Abhängigkeit zum Sauerstoffbedarf der Produktbildner variabel ausgestaltet werden können. Die Gasblasen müssen gleichmässig als möglichst kleine Blasen in die Flüssigkeit eingebracht werden. Durch die flächenmässig anzupassenden Belüftungsschlitze wird diesen Anforderungen entsprochen.In the method according to the invention, the gassing elements are designed such that they can be made variable depending on the oxygen requirement of the product formers. The gas bubbles must be uniformly introduced as the smallest possible bubbles in the liquid. Due to the areal to be adapted ventilation slots these requirements are met.
Die erfindungsgemässe Vorrichtung ist einfach und kostengünstig, da sämtliche Dichtungsprobleme bezüglich der drehenden Rührerwelle zur
Aussenatmosphäre entfallen und ein hermetisch geschlossener Reaktorraum ohne grossen Aufwand sichergestellt werden kann. Die Vorrichtung kann zudem platzsparend ausgestaltet werden, da kein Aussenantrieb benötigt wird.The inventive device is simple and inexpensive, since all sealing problems with respect to the rotating agitator shaft for Outside atmosphere omitted and a hermetically sealed reactor space can be ensured without much effort. The device can also be designed to save space, since no external drive is needed.
Es sind Begasungselemente mit Einsätzen über die Höhe des Reaktors verteilt versehen, die eine dosierte Gaszufuhr ermöglichen.There are gassing elements provided with inserts over the height of the reactor, which allow a metered gas supply.
Die Erfindung wird nachfolgend anhand der Zeichnung näher erläutert. Es zeigen:The invention will be explained in more detail with reference to the drawing. Show it:
Fig. 1 schematisch eine erfindungsgemässe Vorrichtung zum Begasen mit in vier Ebenen übereinander angeordneten Begasungs- bzw. Rührelementen;1 schematically shows an apparatus according to the invention for gassing with gassing or stirring elements arranged one above the other in four planes;
Fig. 2 ein erfindungsgemässes Begasungselement nach Fig. 1 von oben betrachtet; undFIG. 2 shows a gassing element according to the invention according to FIG. 1 viewed from above; FIG. and
Fig. 3 einen Querschnitt durch das Begasungselement nach Fig. 2;3 shows a cross section through the gassing element according to FIG. 2;
Fig. 4 ein Ausführungsbeispiel eines erfindungsgemässen Begasungsbzw. Rührelementes in Seitenansicht; undFig. 4 shows an embodiment of an inventive Begasungsbzw. Stirring element in side view; and
Fig. 5 das Begasungs- bzw. Rührelement nach Fig. 4 in Draufsicht.Fig. 5, the gassing or stirring element of FIG. 4 in plan view.
Fig. l zeigt einen Reaktor 1, der einen zur mikrobiologischen Fermentation und Kultivierung von Zellen vorgesehenen Bioreaktor bildet. Innerhalb des Reaktors 1 ist eine Rührerwelle 2 drehbar angeordnet, die mit ihrem einen Ende in einer Wellenaufhängung bzw. Lagerung 3 gehalten und mit dem anderen in einem Bodenlager 4 gelagert ist. Beim dargestellten Ausführungsbeispiel ist die Wellenaufhängung bzw. Lagerung 3 einem Reaktordeckel Ia zugeordnet.
- A -FIG. 1 shows a reactor 1 which forms a bioreactor intended for microbiological fermentation and cultivation of cells. Within the reactor 1, a stirrer shaft 2 is rotatably arranged, which is held with its one end in a shaft suspension or mounting 3 and supported with the other in a bottom bearing 4. In the illustrated embodiment, the shaft suspension or storage 3 is assigned to a reactor cover Ia. - A -
Auf der als Hohlwelle ausgebildeten Rührerwelle 2 sind mehrere radial verlaufende Begasungselemente 15 bzw. Rührelemente 10 in mehreren Ebenen übereinander angeordnet, vorliegend in drei Ebenen Begasungselemente 15 und in den beiden dazwischenliegenden Ebenen Rührelemente 10. Ausserdem sind vorzugsweise der Innenseite der Reaktorwandung zugeordnete Schickanenelemente 17 vorgesehen, die als Rotationshinderung der Flüssigkeit dienen und mitunter eine Homogenisierung bei niedriger Umdrehungsgeschwindigkeit der Rührerwelle 2 bewirken.On the agitator shaft 2 embodied as a hollow shaft, a plurality of radially extending aeration elements 15 or agitating elements 10 are arranged one above the other in several planes, in this case in three planes aeration elements 15 and in the two intermediate planes agitating elements 10. In addition, smart elements 17 are preferably provided on the inside of the reactor wall. which serve as a rotation prevention of the liquid and sometimes cause homogenization at low rotational speed of the agitator shaft 2.
Bei dem erfindungsgemässen Verfahren sind die Begasungselemente 15 derart ausgebildet, dass sie in Abhängigkeit insbesondere zum Sauerstoffbedarf der durch die Begasung eintretenden Produktebildung variabel gehalten sind und dass sie eine solche Begasung der Flüssigkeit im Reaktor bewirken, dass die Gase gleichmässig in die Flüssigkeit als Mikrobla- sen vorzugsweise mit einem Durchmesser von weniger als einem Millimeter eingebracht werden. Darüberhinaus soll eine homogene Verteilung der Blasen in der Flüssigkeitssäule erfolgen.In the method according to the invention, the gassing elements 15 are designed in such a way that they are kept variable depending on the oxygen requirement of the product formation occurring through the gassing and that such gassing of the liquid in the reactor causes the gases to be uniformly introduced into the liquid as microbubbles preferably be introduced with a diameter of less than one millimeter. In addition, a homogeneous distribution of the bubbles in the liquid column should take place.
Gemäss Fig. 2 und Fig. 3 umfassen die Begasungselemente 15 jeweils einen länglichen Hohlkörper mit annähernd über die gesamte Länge auf der Unter- und Oberseite angeordneten gasdurchlässigen Einsätzen 16. Der ein jeweiliges Begasungselement 15 bildende Hohlkörper mit einem entsprechenden Gaszufuhrkanal 1 1 ist hierbei rohrförmig ausgebildet, so dass das einzublasende Gas bis zum Ende des Hohlkörpers geführt wird. Diese gasdurchlässigen Einsätze 16 sind vorzugsweise aus einem Sintermetall, wie zum Beispiel aus rostfreiem Stahl hergestellt. Sie könnten aber auch aus Keramik oder aus einem Kunststoff bestehen.
Erfindungsgemäss sind diese über die Höhe des Reaktors 1 verteilten Begasungselemente 15 mit Einsätzen 16 versehen, die entweder unterschiedlich grosse Oberflächen oder aber mit unterschiedlichen Porositäten versehen sind, dies in Abhängigkeit insbesondere zum Sauerstoffbedarf der Produktebildner. Zudem ist der hydrostatische Druck der Flüssigkeit zu berücksichtigen. Bei den Begasungselementen 15 sind im unteren Bereich des Reaktors 1 demzufolge grossere Oberflächen bzw. eine grossere Porosität der Einsätze 16 vorzusehen als im oberen Bereich. Die Begasungselemente 15 werden von einem durch die Rührerwelle 2 geführten Gaszufuhrkanal 1 1, 12 mit dem Gas versorgt.According to FIG. 2 and FIG. 3, the gassing elements 15 each comprise an elongated hollow body with gas-permeable inserts 16 arranged approximately over the entire length on the lower and upper side. The hollow body forming a respective gassing element 15 with a corresponding gas supply channel 11 is tubular in this case , so that the gas to be injected is guided to the end of the hollow body. These gas-permeable inserts 16 are preferably made of a sintered metal, such as stainless steel. But they could also be made of ceramic or a plastic. According to the invention, these gassing elements 15 distributed over the height of the reactor 1 are provided with inserts 16, which are provided either with differently sized surfaces or with different porosities, depending in particular on the oxygen requirement of the product formers. In addition, the hydrostatic pressure of the liquid is taken into account. In the case of the gassing elements 15, therefore, larger surfaces or a larger porosity of the inserts 16 are to be provided in the lower region of the reactor 1 than in the upper region. The gassing elements 15 are supplied by a guided through the agitator shaft 2 gas supply channel 1 1, 12 with the gas.
Die von der Rührerwelle 2 radial wegragenden Rührelemente 10 sind auf verschiedenen Ebenen angeordnet. Sie könnten im Prinzip auch mit Einsätzen 16 bestückt sein und zugleich als Begasungselemente dienen. Mit ihnen wird die Rührwirkung zur Homogenisierung des Reaktorinhaltes gewährleistet, wobei eine geringe Umdrehungsgeschwindigkeit (5 bis 100 U/min) gewählt werden kann, da bei dem gegenständlichen Verfahren eine Dispergierung der Gasblasen nicht notwendig ist.The stirring elements 10 projecting radially away from the agitator shaft 2 are arranged at different levels. In principle, they could also be equipped with inserts 16 and at the same time serve as gassing elements. With them, the stirring effect for homogenization of the reactor contents is ensured, with a low rotational speed (5 to 100 U / min) can be selected, since in the subject method, a dispersion of the gas bubbles is not necessary.
Im Weiteren ist im Rahmen der Erfindung im oberen Bereich des Reaktors 1 ein Antriebsorgan 20 mit einem am Ende befestigten Flügelteil 20a und einer separaten Gas und/oder Luftzufuhr 21 versehen, mit welchem diese Rührerwelle 2 drehbar ist. Dieser Flügelteil 20a weist mindestens eine, gegebenenfalls drei Rückstossdüsen 22 auf, die im wesentlichen in Um- fangsrichtung der Rührerwelle 2 gerichtet sind. Der mit den Rückstossdüsen 20 versehene Flügelteil 20a ist jeweils über den separaten Gaszufuhrkanal 21 an einen, durch die drehende Rührerwelle 2 geführten vertikalen Gaszufuhrkanal 23 angeschlossen, der seinerseits über eine Umsetzeinheit
13 mit einer in einer Reaktorwand Ib ortsfest eingebauten Gaszufuhrleitung 24 in Verbindung steht.Furthermore, within the scope of the invention in the upper region of the reactor 1, a drive member 20 is provided with a wing portion 20a fixed at the end and a separate gas and / or air supply 21 with which this agitator shaft 2 is rotatable. This wing part 20a has at least one, optionally three recoil nozzles 22, which are directed in the circumferential direction of the agitator shaft 2 substantially. The wing part 20a provided with the recoil nozzles 20 is connected in each case via the separate gas supply channel 21 to a vertical gas supply channel 23 guided by the rotating agitator shaft 2, which in turn has a transfer unit 13 is in communication with a stationary in a reactor wall Ib installed gas supply line 24.
Über diesen separaten Gaszufuhrkanal 24 kann von einer Druckgasquelle Gas in einer derartigen Menge und unter einem solchen Druck in den Flügelteil 20a eingeführt werden, dass das aus den Rückstossdüsen 20 austretende Gas einen Vortrieb des ganzen Rührers, d.h. aller mit der Rührerwelle 2 drehfest verbundenen Rühr- und/oder Begasungselemente 10, 15 bewirkt. Die benötigte Gasmenge und der Gasdruck als Impulsgeber für den Vortrieb werden in der Kombination der ausserhalb stattfindenden Gasmengeregulierung in Abstimmung mit einem entsprechenden Düsenquerschnitt erzielt.Through this separate gas supply channel 24, gas may be introduced into the wing portion 20a from a pressurized gas source in such an amount and under such a pressure that the gas exiting the recoil nozzles 20 promotes propulsion of the entire agitator, i. all with the agitator shaft 2 rotatably connected stirring and / or gassing elements 10, 15 causes. The required amount of gas and the gas pressure as a pulse generator for the propulsion are achieved in the combination of the outside taking place Gasmengeregulierung in coordination with a corresponding nozzle cross-section.
Somit kann zumindest bei Bioreaktoren, die für Laborzwecke oder für kleinere Produktionseinheiten vorgesehen sind, der Antrieb der mit den Rühr- und/oder Begasungselementen versehenen Rührerwelle 2 allein über die den Vortrieb bewirkenden Rückstossdüsen 20 erfolgen, und die Rührerwelle 2 braucht nicht durch die Reaktorwand hindurch zu einem Aus- senantrieb geführt werden. Sie befindet sich innerhalb des Reaktors 1, in der Wellenaufhängung 3 gehalten und im Bodenlager 4, beispielsweise einem Teflonlager geführt. Der Bioreaktor ist hermetisch geschlossen. Die in den Reaktor 1 mündenden und in der Reaktorwand bzw. im Reaktormantel Ib ortsfest eingebauten, vorzugsweise eingeschweissten Gaszufuhrleitungen 14, 24 stellen keine Gefahr einer undichten Stelle dar.Thus, at least in bioreactors, which are provided for laboratory purposes or for smaller production units, the drive of the agitator shaft 2 provided with the stirring and / or gassing alone on the propulsion causing Rückstossdüsen 20 done, and the agitator shaft 2 does not need through the reactor wall be led to an outside drive. It is located inside the reactor 1, held in the shaft suspension 3 and guided in the bottom bearing 4, for example a Teflon bearing. The bioreactor is hermetically sealed. The opening into the reactor 1 and installed in the reactor wall or in the reactor shell Ib stationary, preferably welded gas supply lines 14, 24 pose no risk of leakage.
Für ganz grosse Produktionseinheiten könnte allenfalls ein zusätzlicher durchtrittsfreier Magnetantrieb vorgesehen sein, d.h. die Rührerwelle 2 könnte über eine an sich bekannte Magnetkupplung (anstelle des Bodenlagers 4) zusätzlich von einem ausserhalb des Reaktors 1 liegenden Motor
angetrieben werden, ohne dabei die Reaktorwand hindurchragen zu müssen.For very large production units, at most an additional penetration-free magnetic drive could be provided, ie the agitator shaft 2 could be via a known magnetic coupling (instead of the bottom bearing 4) additionally from a lying outside of the reactor 1 engine be driven without having to protrude the reactor wall.
Die Flügelteile 10a weisen mit Vorteil eine fluidtechnisch optimierte, aerodynamische Form auf, wie in Fig. 4 und 5 angedeutet. Diese begünstigt die Drehbewegung der Rührelemente 10.The wing parts 10a advantageously have a fluid-technically optimized, aerodynamic shape, as indicated in FIGS. 4 and 5. This favors the rotational movement of the stirring elements 10th
Mit Vorteil kann für den Vortrieb das gleiche Gas eingesetzt werden, das auch zum Begasen der Fermentbrühe vorgesehen ist, z.B. Sterilluft, reiner Sauerstoff oder ein Sauerstoff/Stickstoff-Gemisch.Advantageously, the same gas can be used for propulsion, which is also provided for gassing the fermentation broth, e.g. Sterile air, pure oxygen or an oxygen / nitrogen mixture.
Die erfindungsgemässe Vorrichtung zum Begasen, insbesondere für die mikrobiologische Fermentation und Kultivierung von Zellen in einem geschlossenen Raum, ist einfach und kostengünstig, da sämtliche Dichtungsprobleme bezüglich der drehenden Rührerwelle entfallen und ein hermetisch geschlossener Reaktorraum ohne grossen Aufwand sichergestellt werden kann. Die Vorrichtung kann platzsparend ausgestaltet werden, da kein Aussenantrieb benötigt wird.The device according to the invention for gassing, in particular for the microbiological fermentation and cultivation of cells in a closed space, is simple and inexpensive, since all sealing problems with respect to the rotating agitator shaft are eliminated and a hermetically sealed reactor space can be ensured without much effort. The device can be designed to save space, since no external drive is needed.
Es könnte selbstverständlich bei einer Anwendung eines grosseren Reaktors mehrere solcher erfindungsgemässen Rückstossdüsen verwendet werden. Auch die Anzahl der Begasungs- bzw. Rührelemente kann je nach Grosse des Reaktors variiert werden. Im Prinzip könnten die Einsätze bei den Begasungselementen auch schräg nach unten bzw. oben oder horizontal ausgerichtet sein.
It would of course be used in an application of a larger reactor, several such inventive recoil nozzles. The number of gassing or stirring elements can also be varied depending on the size of the reactor. In principle, the inserts in the gassing elements could also be oriented obliquely downwards or upwards or horizontally.
Claims
1. Verfahren zum Begasen insbesondere für eine mikrobiologische Fermentation und Kultivierung von Zellen in einem geschlossenen Raum, bei dem in einem sterilisierbaren Reaktor (1) über Begasungselemente ein Gas und/oder Luft dosiert eingeblasen wird, wobei in dem Reaktor (1) eine vertikale Rührerwelle (2) mit einer Anzahl von an der Rührerwelle (2) angebrachten, in mehreren Ebenen übereinander angeordneten Begasungs- und/oder Rührelementen (10) angeordnet sind, dadurch gekennzeichnet, dass die Begasungselemente (15) derart ausgebildet sind, dass sie eine solche Begasung der Flüssigkeit im Reaktor bewirken, dass die Gase gleichmäs- sig in die Flüssigkeit als Mikroblasen eingebracht werden.1. A method for gassing in particular for a microbiological fermentation and cultivation of cells in a closed space, in which a gas and / or air is injected metered in a sterilizable reactor (1) via gassing, wherein in the reactor (1) has a vertical stirrer shaft (2) are arranged with a number of attached to the agitator shaft (2) arranged in several levels one above the other gassing and / or stirring elements (10), characterized in that the gassing elements (15) are designed such that they such gassing The effect of the liquid in the reactor is that the gases are introduced uniformly into the liquid as microbubbles.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass die Begasungselemente (15) eine derartige Blasenbildung im Reaktor (1) erzeugen, dass eine homogene Verteilung von feinen Blasen im gesamten Reaktorinhalt erfolgt. 2. The method according to claim 1, characterized in that the gassing elements (15) produce such a bubble formation in the reactor (1), that a homogeneous distribution of fine bubbles throughout the reactor contents.
3. Vorrichtung zur Durchführung des Verfahrens nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass die Begasungselemente (15) jeweils einen länglichen Hohlkörper mit einem annähernd über die gesamte Länge auf der Unter- und/oder Oberseite angeordneten gasdurchlässigen Einsatz (16) aufweisen.3. Apparatus for carrying out the method according to claim 1 or 2, characterized in that the gassing elements (15) each have an elongated hollow body with an approximately over the entire length arranged on the bottom and / or top gas-permeable insert (16).
4. Vorrichtung nach Anspruch 3, dadurch gekennzeichnet, dass der ein jeweiliges Begasungselement (15) bildende Hohlkörper rohrförmig ausgebildet ist und der oder die gasdurchlässigen Einsätze (16) aus einem Sintermetall, aus Keramik oder aus Kunststoff bestehen.4. Apparatus according to claim 3, characterized in that the respective a gassing element (15) forming hollow body is tubular and the or the gas-permeable inserts (16) made of a sintered metal, ceramic or plastic.
5. Vorrichtung nach Anspruch 4, dadurch gekennzeichnet, dass die über die Höhe des Reaktors (1) verteilten Begasungselemente (15) mit Einsätzen (16) versehen, die entweder unterschiedlich grosse Oberflächen und/oder aber mit unterschiedlichen Porositäten versehen sind, dies in Abhängigkeit des hydrostatischen Druckes der zu fermentierenden bzw. kultivierenden Flüssigkeit im Reaktor.5. The device according to claim 4, characterized in that over the height of the reactor (1) distributed gassing elements (15) with inserts (16) provided either different sized surfaces and / or are provided with different porosities, this in dependence the hydrostatic pressure of the liquid to be fermented or cultured in the reactor.
6. Vorrichtung zur Durchführung des Verfahrens nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass für den Vortrieb der an der drehbar gelagerten Rührerwelle (2) angebrachten Begasungs- bzw. Rührelemente (10) wenigstens eine an mindestens einen Gaszufuhrkanal (11, 12, 14) angeschlossene Rückstossdüse (20) vorhanden ist.6. A device for carrying out the method according to claim 1 or 2, characterized in that for the propulsion of the rotatably mounted agitator shaft (2) mounted gassing or stirring elements (10) at least one at least one gas supply channel (11, 12, 14 ) connected recoil nozzle (20) is present.
7. Vorrichtung nach Anspruch 6, dadurch gekennzeichnet, dass für das Antriebsorgan (20) der Rührerwelle (2) zumindest eine Rückstossdüse (22) vorgesehen ist, wobei die Rückstossdüse (22) jeweils einem am Ende des von der Rührerwelle (2) wegragenden Flügelteils (20a) zugeordnet ist und an einen separaten Gaszufuhrkanal (24) angeschlossen ist. 7. Apparatus according to claim 6, characterized in that for the drive member (20) of the agitator shaft (2) at least one Rückstossdüse (22) is provided, wherein the Rückstossdüse (22) each one at the end of the agitator shaft (2) projecting wing part (20a) and is connected to a separate gas supply channel (24).
8. Vorrichtung nach Anspruch 7, dadurch gekennzeichnet, dass das für den Vortrieb des Antriebsorganes (20) vorgesehene Gas in benötigter Menge und unter einem vorgegebenen Druck von einer Druckgasquelle über eine in einer Reaktorwand (Ib) ortsfest eingebaute Gaszufuhrleitung und eine Umsetzeinheit (13) in einen durch die drehbare Rührerwelle (2) geführten Gaszufuhrkanal (23) einführbar ist, wobei dieser vertikale Gaszufuhrkanal (23) jeweils über einen zur Rührerwelle (2) radial gerichteten Gaszufuhrkanal (21) mit dem die Rückstossdüse (22) aufweisenden Flügelteil (20a) verbunden ist.8. The device according to claim 7, characterized in that the for the propulsion of the drive member (20) provided gas in the required amount and under a predetermined pressure from a compressed gas source via a in a reactor wall (Ib) fixedly installed gas supply line and a transfer unit (13) in a through the rotatable agitator shaft (2) guided gas supply channel (23) is insertable, said vertical gas supply channel (23) via a respective agitator shaft (2) radially directed gas supply channel (21) with the Rückstossdüse (22) having wing portion (20a) connected is.
9. Vorrichtung nach Anspruch 7 oder 8, dadurch gekennzeichnet, dass die Flügelteile (20a) eine die Drehbewegung des Rührelemente (10) begünstigende aerodynamische Aussenform aufweisen.9. Apparatus according to claim 7 or 8, characterized in that the wing parts (20a) have a rotational movement of the stirring elements (10) favoring aerodynamic outer shape.
10. Vorrichtung nach einem der Ansprüche 6 bis 9, dadurch gekennzeichnet, dass die Rührerwelle (2) im Innern des Reaktors (1) untergebracht und dabei zum einen in einer Wellenaufhängung bzw. Lagerung (3) gehalten und zum andern in einem Bodenlager (4) gelagert ist.10. Device according to one of claims 6 to 9, characterized in that the agitator shaft (2) accommodated in the interior of the reactor (1) and held on the one hand in a shaft suspension or storage (3) and on the other in a bottom bearing (4 ) is stored.
11. Vorrichtung nach einem der Ansprüche 6 bis 10, dadurch gekennzeichnet, dass die Rührerwelle (2) im Innern des Reaktors (1) untergebracht und dabei mit einem Ende in einer Wellenaufhängung bzw. Lagerung (3) gehalten und am anderen Ende über eine magnetische Kupplung mit einem externen Hilfsantrieb wirkverbunden ist. 11. Device according to one of claims 6 to 10, characterized in that the agitator shaft (2) housed inside the reactor (1) and held at one end in a shaft suspension or storage (3) and at the other end via a magnetic Coupling is operatively connected to an external auxiliary drive.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH01702/06A CH698723B1 (en) | 2006-10-25 | 2006-10-25 | Device for gassing, and in particular for the microbiological fermentation and cultivation of cells. |
PCT/EP2007/009274 WO2008049617A1 (en) | 2006-10-25 | 2007-10-25 | Method and device for aeration, particularly for microbiological fermentation and for cell cultivation |
Publications (1)
Publication Number | Publication Date |
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EP2084260A1 true EP2084260A1 (en) | 2009-08-05 |
Family
ID=38921720
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP07819323A Withdrawn EP2084260A1 (en) | 2006-10-25 | 2007-10-25 | Method and device for aeration, particularly for microbiological fermentation and for cell cultivation |
Country Status (5)
Country | Link |
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US (1) | US9399203B2 (en) |
EP (1) | EP2084260A1 (en) |
CN (1) | CN101573436B (en) |
CH (1) | CH698723B1 (en) |
WO (1) | WO2008049617A1 (en) |
Families Citing this family (19)
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CN102233245B (en) * | 2011-07-13 | 2013-03-27 | 浙江长江搅拌设备有限公司 | Gas, solid and liquid stirring machine with high-efficiency flexible structure |
US9700857B1 (en) | 2012-03-23 | 2017-07-11 | Life Technologies Corporation | Fluid mixing system with drive shaft steady support |
CN103045472A (en) * | 2013-01-25 | 2013-04-17 | 李明忠 | Pneumatic stirring machine for biological fermentation |
CN105642213A (en) * | 2014-11-14 | 2016-06-08 | 程叶红 | Microemulsion reaction kettle for producing chemical biosurfactant microemulsion |
CN105664819A (en) * | 2014-11-14 | 2016-06-15 | 程叶红 | Microemulsion reactor for biological surfactant microemulsion production |
EP3031895A1 (en) * | 2014-12-12 | 2016-06-15 | Universitat Autònoma de Barcelona | Aeration and agitation system for the culture of microorganisms in single use bioreactors |
WO2016092073A1 (en) * | 2014-12-12 | 2016-06-16 | Universitat Autonoma De Barcelona | Coupled systems of aeration, agitation and heat exchange for the culture of microorganisms in single use bioreactors |
SG11201705016VA (en) * | 2014-12-31 | 2017-07-28 | Ge Healthcare Bio-Sciences Corp | Shaft-mounted fluid transfer assembly for a disposable bioreactor |
CN106076161A (en) * | 2016-04-28 | 2016-11-09 | 柳江县科益搪瓷有限公司 | Agitating device for culture medium of edible fungus |
EP3485968B1 (en) * | 2016-06-15 | 2024-07-31 | Satoshi Anzai | Ultrafine bubble generation device for aquaculture or wastewater treatment |
CN106902689B (en) * | 2017-04-28 | 2023-08-22 | 山东金祥云贸易有限公司 | Brick making mixing device |
WO2018209133A1 (en) * | 2017-05-12 | 2018-11-15 | Jerry Shevitz | Bioreactors |
CN108913595B (en) * | 2018-08-03 | 2023-10-03 | 滕海峰 | Plant energy supply device |
CN109182098A (en) * | 2018-10-10 | 2019-01-11 | 南京和润隆环保科技有限公司 | A kind of methane-generating pit with Stirring pipeline |
CN109439516A (en) * | 2018-12-20 | 2019-03-08 | 巫溪县清味鲜食品有限公司 | A kind of fully automatic electric cooker that can make fermented glutinour rice |
CN110042046B (en) * | 2019-05-07 | 2022-10-04 | 南京工业大学 | Continuous immobilized internal stirring micro-membrane aeration internal circulation airlift bioreactor |
CN111826268A (en) * | 2020-07-22 | 2020-10-27 | 湖南广盛源医药科技有限公司 | A fermenting installation for production of medical alcohol |
CN116120103B (en) * | 2023-03-23 | 2023-06-23 | 浙江大学 | Aeration-promoting oxygen supply device and method for garbage fermentation |
CN117736846A (en) * | 2023-12-28 | 2024-03-22 | 石家庄永宸生物科技有限公司 | Fermenting installation is used in bean flour production |
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CH663422A5 (en) * | 1982-05-27 | 1987-12-15 | Chemap Ag | METHOD AND FERMENTER FOR GROWING TISSUE CELLS. |
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US5779996A (en) * | 1995-04-21 | 1998-07-14 | Innovative Biosystems, Inc. | Microbial remediation reactor and process |
FR2784311B1 (en) * | 1998-10-09 | 2000-12-08 | Air Liquide | DEVICE FOR AGITATING A LIQUID IN A REACTOR AND FOR INJECTING A GAS IN THIS LIQUID |
CH696494A5 (en) * | 2003-04-30 | 2007-07-13 | Andreas Kloss | A device for the microbiological fermentation and cultivation of cells. |
EP1473358A3 (en) * | 2003-04-30 | 2005-06-08 | Chemie- Und Tankanlagenbau Reuther Gmbh | Method and device for gassing and stirring materials |
DE102004062703A1 (en) * | 2004-12-21 | 2006-06-22 | Henkel Kgaa | Mixing container for mixing liquids with liquids, solids and/or gases comprises current breakers arranged on base of boiler or on lid to rotate about vertical axis |
DE502006008529D1 (en) * | 2005-10-03 | 2011-01-27 | Zeta Biopharma Gmbh | DIRECTIONS WITH STIRRER |
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2006
- 2006-10-25 CH CH01702/06A patent/CH698723B1/en not_active IP Right Cessation
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- 2007-10-25 WO PCT/EP2007/009274 patent/WO2008049617A1/en active Application Filing
- 2007-10-25 US US12/446,823 patent/US9399203B2/en not_active Expired - Fee Related
- 2007-10-25 CN CN2007800396399A patent/CN101573436B/en not_active Expired - Fee Related
- 2007-10-25 EP EP07819323A patent/EP2084260A1/en not_active Withdrawn
Non-Patent Citations (1)
Title |
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Also Published As
Publication number | Publication date |
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US20100178685A1 (en) | 2010-07-15 |
CN101573436A (en) | 2009-11-04 |
CH698723B1 (en) | 2009-10-15 |
WO2008049617A1 (en) | 2008-05-02 |
US9399203B2 (en) | 2016-07-26 |
CN101573436B (en) | 2012-12-19 |
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