Integrated gas introduction and agitation unit for gas-liquid reactors

Abstract

The invention relates to a gas charging unit for bubble-free introduction of a process gas into a liquid located in a reactor, wherein the gas charging unit comprises at least: - a first gas receiving chamber and a second gas receiving chamber spaced apart therefrom for receiving a process gas, the two gas receiving chambers being connected to one another by at least two two-dimensional, gas-conducting diffusion membranes comprising hollow fibers spaced apart from one another and at least partially fixed to one another; - a container for gas supply on at least one of the gas receiving chambers; - a container for a shaft on at least one of the gas receiving chambers; wherein the gas charging unit for charging a liquid in the reactor can be supplied with a process gas by means of the gas supply container, can be set into rotary motion by means of the container for a shaft, and can form a convective flow within the reactor by means of the rotary motion of the gas charging unit in the liquid. Furthermore, the invention relates to a method for charging a process liquid, a gas-liquid reactor comprising a gas charging unit according to the invention and the use of a gas charging unit according to the invention for supplying a bioculture with a process gas.

Description

Technical Field

[0001] This invention relates to an aeration unit for introducing process gas into a liquid located in a reactor without bubbles, wherein the aeration unit comprises at least:

[0002] - A first gas receiving chamber and a second gas receiving chamber spaced apart therefrom for receiving process gases, the two gas receiving chambers being connected to each other by at least two two-dimensional, gas-conducting diffusion membranes comprising hollow fibers spaced apart from each other and at least partially fixed to each other;

[0003] - A container for gas supply on at least one of the gas receiving chambers;

[0004] - A container for the shaft on at least one of the gas receiving chambers;

[0005] The aeration unit for aerating the liquid in the reactor can supply process gas through the gas supply container, can be configured to rotate through the container for the shaft, and can form convective flow within the reactor through the rotational movement of the aeration unit in the liquid. Furthermore, the present invention relates to a method for aerating process liquids, a gas-liquid reactor including the aeration unit according to the invention, and the use of the aeration unit according to the invention for supplying process gas to biological cultures. Background Technology

[0006] Today, the reliable production of essential basic materials through more sustainable methods is increasingly becoming a focus of public attention. This approach involves not only the production methods themselves but also extends to the properties of the substances used after their planned lifespan. Particularly evident in recent decades is the growing development of alternative and bioproduct variants for a wide range of chemicals synthesized from petroleum, promising not only more resource- and energy-efficient production processes but also improved chemical and biological properties of the produced substances, such as faster degradation.

[0007] This approach is particularly suitable for surfactant biomolecules, as these substances have a lasting environmental impact, and their added value in cosmetics or pharmaceuticals can offset the still relatively high production costs. A more environmentally friendly manufacturing alternative is a fermentation process based on biological systems, where renewable feedstocks serve as the nutrient medium and are carried out under oxygen input. However, a drawback is that in the biosynthesis of proteins and surfactants, fermenters often generate significant amounts of foam, which is detrimental to performance and the overall process. To date, the preferred method for aeration of these systems has been bubble aeration followed by bubble destruction by agitators or the use of defoamers. This should ensure bubble-free fermentation without loss of biomass. However, bubble aeration involving bubble bursting is disadvantageous because further control parameters complicate process control, and mechanical foam destruction significantly increases the energy costs of the process. Foam inhibitors are not a sustainable alternative because additional purification in downstream processes strongly impacts process costs. In this regard, existing fermentation methods and the equipment used for them need improvement to ensure simple and reproducible fermentation processes without foam formation.

[0008] Some methods for aerating fermentation broth without bubbles can also be found in patent literature.

[0009] For example, DE 10 2006 008 687 A1 describes a process for aerating a liquid, particularly in biotechnology, especially in cell culture, through gas exchange via one or more submerged membrane surfaces such as tubes, cylinders, or modules, characterized in that the membrane surface undergoes any rotational oscillating motion in the liquid.

[0010] In addition, DE 44 046 00 C1 discloses a process for bubble-free aeration of microorganisms fixed on a carrier material in a reactor, wherein the carrier material with microorganisms is passed upstream of the carrier material by an oxygen-rich aqueous solution through a membrane containing oxygen gas applied on one side.

[0011] In another patent document, DE 41 42 502 A1, a process for introducing hydrogen into an aqueous liquid without bubbles is disclosed, wherein hydrogen is introduced into the aqueous liquid via a membrane. This process is characterized by using a membrane comprising: a) a support structure formed of a porous polymer, and b) at least one layer of non-porous polymer, wherein the aqueous liquid contacts the membrane on one side of the non-porous polymer layer.

[0012] Such solutions known in the prior art can offer further improvement potential, particularly in the efficiency of supplying process gases to process liquids, and especially in reliably preventing foam formation, even for systems with difficult product characteristics. Summary of the Invention

[0013] Therefore, the object of the present invention is to at least partially overcome the disadvantages known in the prior art. In particular, the object of the present invention is to provide an aeration unit and a gas-liquid reactor having the aeration unit, characterized by a particularly efficient and uniform gas supply to the process liquid, significantly reducing foam formation during the supply process.

[0014] According to the present invention, this task is accomplished by an aeration unit for introducing process gas into a liquid located in a reactor without bubbles, wherein the aeration unit comprises at least:

[0015] - A first gas receiving chamber and a second gas receiving chamber spaced apart therefrom for receiving process gases, the two gas receiving chambers being connected to each other by at least two two-dimensional, gas-conducting diffusion membranes comprising hollow fibers spaced apart from each other and at least partially fixed to each other;

[0016] - A container for gas supply on at least one of the gas receiving chambers;

[0017] - A container for the shaft on at least one of the gas receiving chambers;

[0018] The aeration unit for aerating the liquid in the reactor can supply process gas through the gas supply container, can be configured to rotate through the container for the shaft, and can form convective flow in the reactor through the rotational movement of the aeration unit in the liquid.

[0019] Surprisingly, the above design has yielded an extremely efficient and flexible aeration-stirring combination suitable for a wide range of aeration applications in various (bio)reactors. Process gases are introduced into the process liquid in a highly uniform and gentle manner. Due to the combination of simultaneous aeration and stirring surfaces, large quantities of process gases can be uniformly introduced into the liquid through the exchange surface. This is particularly due to the use of membrane exchange surfaces made of hollow fibers, which are always actively released from the diffused process gases through continuous movement within the liquid. Therefore, on the one hand, the hollow fiber membranes used in the design according to the invention achieve a larger exchange surface than currently known in general; on the other hand, they are even more efficient than prior art solutions because the simultaneous movement of the sheared gas at the membrane surface completely avoids diffusion blockage caused by adhering bubbles. Moreover, the design is very robust due to the central supply of process gases and the uniform distribution of gas in the gas receiving chamber, allowing for high-speed and thus strong convection through the firmly anchored hollow fibers. The combination of aeration and stirring also ensures that the hollow fibers are flowed through the process liquid not only indirectly but also actively. The module itself does not generate dead zones, which contributes to improved supply efficiency and uniformity of liquid aeration. Furthermore, shearing keeps bubble size small. Therefore, even challenging fermentation tasks involving live cultures can be handled, such as in the production of foam-promoting substances, where uniformity of supply, absolute gas quantity, and control over bubble size through simultaneous shearing prevent the formation of bubbles and / or excessive foaming in liquid media. The aeration unit can also be composed of any number of aeration units connected in series, which facilitates the cleaning and sterilization of individual modules and allows for design expansion to larger reactor volumes.

[0020] The aeration unit according to the invention is suitable for introducing process gas into the liquid in a reactor without bubbles. The process liquid in the reactor can be simultaneously agitated and supplied with process gas by the aeration unit according to the invention. This means that the process gas is introduced into the process liquid continuously or discontinuously at time intervals via the aeration unit. The introduction of the process gas at least temporarily increases the concentration of the process gas in the liquid in the reactor and at the supply point. The process gas may include oxygen, nitrogen, carbon dioxide, carbon monoxide, hydrogen, or similar gases or mixtures thereof. Typically, the process gas forms reactants for further chemical reactions in the process fluid. The structure according to the invention allows the process gas to be supplied to the process fluid without bubbles. In the sense of the invention, "bubble-free" means that the bubble size of the process gas on the membrane surface is within a range that is invisible to the naked eye or difficult to see. For example, the bubble size can be on the order of a few micrometers. The design according to the invention particularly prevents the formation or deposition of foam on the surface of the process liquid during the process. The liquid in the reactor can be, for example, an aqueous solution, a dispersion, or an emulsion. However, this entry is not limited to aqueous systems. Non-aqueous liquid systems can also be aerated without bubbles.

[0021] The gas supply unit includes at least a first gas receiving chamber and a second gas receiving chamber spaced apart therefrom for receiving process gases. Process gases can be supplied to one of the two gas receiving chambers via a gas supply line and are uniformly distributed therein. The gas receiving chamber forms a reservoir for the process gases and can also compensate for possible pressure fluctuations compared to direct supply to the membrane. The process gases are then supplied from the first gas receiving chamber through a hollow fiber membrane to the second gas receiving chamber, wherein the distance between the two receiving chambers can be selected based on the reactor size, the length and mechanical stability of the hollow fibers, the required gas input, and the required hemodynamics. Such gas receiving chambers can be made of, for example, metal or plastic and have rotational symmetry. Both gas receiving chambers also have containers for the hollow fiber membranes, which allow each hollow fiber membrane to be independently secured. The containers for the hollow fiber membranes can, for example, consist of grooves in the surface of the gas receiving chambers, where the hollow fiber membranes can be mechanically clamped or glued together and thus connected to the gas receiving chambers in an airtight manner.

[0022] Two gas receiving chambers are interconnected by at least two two-dimensional gas-conducting diffusion membranes made of hollow fibers, which are spaced apart from each other and at least partially fixed to one another. Thus, the process gas is introduced into the liquid not through the gas receiving chambers but through the hollow fiber membranes, which are connected to the two gas receiving chambers in a gas-conducting manner. The hollow fibers are not used individually. Several hollow fibers are arranged adjacent to or behind each other, thus forming a flat membrane by the arrangement of the hollow fibers. To further stabilize the membrane, individual hollow fibers can also be fixed to each other by further mechanical means. For example, individual hollow fibers can be stabilized relative to each other in the form of a fabric with non-gas-carrying threads or fibers extending perpendicularly or substantially perpendicular to the hollow fibers. For example, each cm of hollow fiber membrane can be fitted with a fixation element in the form of preferably one, more preferably two, more preferably three inert polymer threads, which alternately pass above and below the hollow fibers and fix the hollow fibers relative to each other. A diffusion membrane or microfiltration membrane is a membrane in which gas first diffuses into the membrane and then passes through the hollow fiber shell before entering the process liquid. Membranes can be dense or porous, with a porosity within a certain range to prevent concentration polarization outside the membrane—and the associated degassing of gases introduced in the form of bubbles—when there is sufficient flow. The possible pore size range for non-"dense" membranes is 20 nm to 20 µm. "Dense" diffusion membranes can have multilayer structures. This allows additional layers to prevent process fluids from entering the membrane, or, if desired, to prevent unwanted gases from backdiffusing into the membrane. Furthermore, layered composite structures ensure that extremely thin, dense material films can be supported on layers with high mechanical strength, such as porous PMPs, which are active layers for example, PMP, TMCTS, or PDMS / silicone. This thin, dense layer is crucial for the permeability of the gases used. The thinnest possible layer ensures high mass transfer. For dense membranes, the ratio of mass transfer through the membrane to its thickness is inversely proportional. However, thin active layers are often mechanically unstable and require a carrier, i.e., a support. The most porous possible support provides negligible resistance to gas entry into the process fluid. The hollow fibers that can be used can be, for example, made of PMP (polymethylpentene) and have an inner diameter of 0.2 mm and an outer diameter of 0.38 mm. PDMS (polydimethylsiloxane) / silicone films with an inner diameter of about 0.3 mm and an outer diameter of about 0.5 mm can also be used. Preferably, in order to form a planar film arrangement from individual hollow fibers, more than 50, more preferably more than 100, and more preferably more than 500 hollow fibers are arranged adjacent to or after each other. This planar arrangement results in preferably more than 40%, more preferably more than 50%, and more preferably more than 60% of the area between two spaced-apart, non-directly adjacent hollow fibers being covered by additional hollow fibers.This planar arrangement can be achieved, for example, by fixing hollow fibers with the aforementioned dimensions at a distance between them in the gas receiving chamber that is greater than or equal to 0.05 mm and less than or equal to 2.5 mm, more preferably greater than or equal to 0.1 mm and less than or equal to 1 mm. Gas flows through the gas receiving chamber into the hollow fibers connected together to form a membrane, and enters the liquid phase outside the fibers by a driving force.

[0023] The gas-filling unit comprises at least two diffusion membranes. This means that, starting from the gas receiving chamber, not only does one membrane of multiple hollow fibers with continuous gas paths extend into the process liquid in the second gas receiving chamber, but at least two membranes of multiple hollow fibers spaced apart from each other are arranged in the first gas receiving chamber, which can supply gas to the process liquid through separate gas paths. Preferably, there may be separate membrane regions of more than 10, more preferably more than 50, and even more preferably more than 100 hollow fibers arranged from the first gas receiving chamber into the process liquid.

[0024] Individual hollow fibers can be attached to a gas receiving chamber by mechanically clamping the hollow fibers in a specially designed device or by incorporating a membrane into such a gas receiving chamber. Preferably, an individual hollow fiber membrane is incorporated into the gas receiving chamber.

[0025] A container for gas supply is located on one of the gas receiving chambers. The gas receiving chamber can be supplied with process gas from the outside via a supply line through the reactor. For this purpose, an external gas source can be supplied into the interior of the reactor to the gas receiving chamber via a hose or capillary system. There, the hose or capillary can be connected to the container of the gas receiving chamber designed for this purpose. This can be done in an airtight manner, for example, via a fitting. Preferably, a metric flangeless flat-bottomed connecting element with a flangeless collar can be used as the fitting. The fitting can be made of, for example, metal or plastic, such as PEEK. The fitting can be arranged centrally or non-centrally on the gas receiving chamber; advantageously, the fitting is arranged on the side of the gas receiving chamber facing the hollow fiber membrane. Depending on the operating mode of the gas supply unit, only one or two gas receiving chambers may be equipped with containers for gas supply. In particular, it is possible for the gas filling unit to operate in two modes. On the one hand, the gas supply can operate in a “crossflow” mode, or alternatively in a “dead-end” mode. In the “dead-end” mode, gas is only delivered to the gas receiving chamber of the gas filling unit. In this mode, emissions of process gases that have not yet been introduced, such as those in another gas receiving chamber, do not need to be collected.

[0026] A container for the shaft is located on one of the gas receiving chambers. One of the gas receiving chambers includes a device for receiving the shaft to input the mechanical energy required to power the moving gas supply unit. The shaft can be guided through the reactor and connected to a drive or gearbox, which allows the shaft to rotate. Rotating the shaft also rotates the aeration unit and allows the process fluid to move through the planar hollow fiber membrane. The movement of the shaft, and therefore the movement of the aeration unit, can be in only one direction or preferably in two directions. Thus, constant or alternating directions of rotation of the aeration units with different speeds can be achieved.

[0027] Process gas can be supplied to the aeration unit through the gas supply inlet to aerate the liquid in the reactor. This allows the aeration unit to be set to rotational motion via the shaft inlet, and convection is created within the reactor through the rotational motion of the aeration unit in the liquid. Mechanical energy and process gas can be transferred to the aeration unit through both the gas and shaft inlets. The process gas is released into the process liquid through a hollow fiber membrane, and directional flow is generated within the liquid in the reactor through the rotational motion of the aeration unit—which is actually a flat hollow fiber membrane.

[0028] In a preferred embodiment of the aeration unit, the projection of the diffusion membrane onto the gas receiving chamber can have an arcuate geometry. To achieve a uniform flow distribution within the reactor liquid and for uniform overflow of the individual hollow fibers within the aeration unit, it has proven particularly suitable that the individual hollow fibers are spaced apart from each other rather than arranged in a straight line along both the longitudinal and transverse directions on the gas receiving chamber. Thus, within the planar design framework of the membrane, the result is not a straight surface of the arranged hollow fibers but a curved surface. In addition to improved flow distribution and uniformity, this design can particularly facilitate improved gas entry into the liquid by uniformly shearing bubbles from the surface of the hollow fiber membrane. In particular, it can also completely delay or prevent the formation of larger bubbles on the membrane surface. Possible embodiments of the arcuate geometry are shown in the figures. Preferably, the arc can have a diameter greater than or equal to 1 m. -1 And less than or equal to 100 m -1 The curvature is further preferably greater than or equal to 5 m. -1 And less than or equal to 70 m -1 .

[0029] In a further preferred embodiment of the gas supply unit, the container for gas supply and the container for the shaft can be arranged in only one gas receiving chamber. To balance the flow distribution in the reactor, it has proven particularly advantageous to arrange the inlet and the connection for the drive shaft in the center of only one gas receiving chamber. More preferably, the gas container and the shaft container can be designed together, for example, in the form of a hollow shaft, such that both containers are located within a single connection on the gas supply unit. This can help reduce the number of mechanical parts on the gas supply unit. Furthermore, this combined port can preferably be designed in the center of the gas supply unit. Preferably, process gas and the necessary kinetic energy can be supplied to the gas supply unit simultaneously through only one combined container on one of the gas receiving chambers. This can maintain a particularly uniform flow distribution in the gas supply unit and reduce equipment connection work. The latter can also help improve the cleanability and sterilizability of the gas supply unit.

[0030] In a further preferred aspect of the aeration unit, the two gas receiving chambers can each be cylindrical and interconnected by one or more mechanical supports. The rotationally symmetric cylindrical geometry has been found particularly advantageous for creating the most efficient convection possible within most reactor geometries. This design of the gas receiving chambers allows for the repeatable induction of very uniform and strong flow within the aeration unit and the reactor itself, which facilitates a particularly good supply of process gas to the process liquid. In addition to fixing the relative positions of the two gas receiving chambers relative to each other by hollow fiber membranes, fixing their relative positions by one or more mechanical supports has also proven advantageous. This measure reduces synchronization and unwanted oscillations of the aeration unit at high speeds. Preferably, the supports can be guided through the center of the two cylindrical gas receiving chambers. Such an implementation improves the flow distribution within the aeration unit, and particularly between the individual hollow fiber membranes.

[0031] According to preferred features of the aeration unit, at least one retaining disc can be arranged between two gas receiving chambers on the mechanical support, the retaining disc being designed to mechanically hold the diffusion membrane. It has proven particularly advantageous to position the retaining disc between the two gas receiving chambers on the support, with the disc in mechanical contact with the hollow fiber membrane, in order to create mirror-symmetric convective flow within a wide range of reactor geometries. The hollow fiber membranes can be mechanically held "loosely" by the retaining disc, or they can be stretched or twisted away from the roll-off line by the retaining disc. In the former case, holding the hollow fiber membrane in place also allows for greater mechanical forces, for example, due to higher circulation rates of the aeration unit, without the risk of membrane damage. More fragile hollow fibers can generally be used. However, in addition to the mechanical task of holding the membrane, the achievable flow geometry can also be influenced by the retaining disc. Individual hollow fiber membranes can be selectively deflected or twisted into a geometry predetermined by their connection to the gas receiving chambers. This deflection alters the planar geometry of the membrane and may result in specific convection patterns in the fluid. In this way, the membrane can be tailored to specific aeration tasks and reactor geometries.

[0032] In a preferred embodiment of the gas supply unit, the mechanical support may be adapted to deliver the process gas out of the gas receiving chamber. To enable the gas supply device to be designed as compactly as possible and to improve unit supply in cross-flow operation, a hollow shaft form of mechanical support has proven particularly suitable, which can also deliver the process gas into and out of the gas receiving chamber.

[0033] In a further preferred embodiment of the gas supply unit, the area ratio of the total cross-sectional area of ​​the hollow fibers to the cross-sectional area of ​​the gas receiving chamber can be greater than or equal to 5% and less than or equal to 45%. The proposed design provides a compact inflation unit with a significantly larger process gas exchange area compared to prior art solutions. These large exchange areas exhibit only a low-tendency bubble formation and also create more favorable flow behavior for the inflation unit. The total hollow fiber cross-sectional area is calculated by multiplying the cross-section of a single hollow fiber by the number of fibers arranged on the gas receiving unit. The cross-sectional area of ​​the gas receiving chamber is derived from the area of ​​the gas receiving chamber supplied with process gas. Even if the gas receiving chamber includes a central or outer surface that cannot be attached to the hollow fiber membrane due to a lack of process gas supply, this surface does not contribute to the aforementioned ratio. In a preferred embodiment, the area ratio can be greater than or equal to 7.5% and less than or equal to 20%, more preferably greater than or equal to 10% and less than or equal to 15%. Within these ratios of the inflation exchange area and the gas receiving chamber, a large amount of process gas can be introduced under uniform flow conditions.

[0034] In a further preferred embodiment of the inflation unit, the filling density of the diffusion membrane relative to the volume of the inflation unit, expressed as the surface area of ​​the hollow fiber divided by the volume of the inflation unit, can be greater than or equal to 0.1 cm³. -1 And less than or equal to 7.5 cm -1 In this case, the total surface area of ​​the hollow fibers can be calculated using the number and surface area of ​​the hollow fibers that can freely contact the process fluid. In the case of cylindrical or non-cylindrical geometries, the total volume of the aeration unit is obtained by the volume of the aeration unit that can contact the process liquid between the gas receiving chambers. Using the design according to the invention, a very high active aeration zone can be accommodated in a very small space, which, in addition to the high process gas flow combined with simultaneous stirring, also contributes to the efficient supply of very high reactor volumes. Preferably, this ratio can also be greater than or equal to 0.25 cm⁻¹. -1 And less than or equal to 6 cm -1 Further preferred is a diameter greater than or equal to 0.5 cm. -1 And less than or equal to 3 cm -1 .

[0035] The present invention further provides a method for aerating a process liquid within a reactor, wherein gas is introduced via an aeration unit according to the invention. The process step of aerating the process liquid via the aeration unit according to the invention can have several process advantages. In this process step, a large amount of process gas can be uniformly supplied within the fluid volume, and the combination of agitation and aeration allows for the introduction of little or no very small bubbles. Due to direct contact with the fluid boundary and direct shearing of bubbles from the membrane surface, diffusion inhibition caused by concentration gradient polarization at the hollow fiber surface is avoided, and a larger volume of liquid is supplied to the reactor compared to a fixed arrangement due to the uniform movement of all fibers. In particular, dead zones in the reactor and the aeration unit can be avoided due to the controlled formation of convection in this process step.

[0036] In a preferred embodiment of the method, the rotational speed of the membrane surface at the outermost edge of the inflation unit can be greater than or equal to 0.1 m / s and less than or equal to 5 m / s. With the arrangement according to the invention, even inherently mechanically unstable diffusion membranes can operate at high shear rates in liquids. This is not theoretically constrained because the spaced hollow membrane surfaces are flowed through or covered, thus absorbing only a portion of the liquid's kinetic pulses. Advantageously, this leads to stripping of the diffused process gas and a reduction in mechanical stress. The speed of the inflation unit can be adjusted by the area dimensions of the gas receiving chamber and by the rotational speed of the inflation unit itself. The maximum rotational speed of the hollow fibers is derived from a reference to the hollow fibers furthest from the center of the inflation unit. Therefore, hollow fibers located further inside the inflation unit have low circulation speeds. More preferably, the orbital speed of the membrane surface at the outermost edge of the inflation unit can be greater than or equal to 0.25 m / s and less than or equal to 4 m / s, more preferably greater than or equal to 0.5 m / s and less than or equal to 3 m / s.

[0037] According to the invention, a gas-liquid reactor is further provided, wherein the gas-liquid reactor comprises at least a reactor shell, a drive unit, a gas supplier, and an aeration unit according to the invention. The reactor according to the invention is a gas-liquid reactor for bubble-free aeration of a process liquid with a process gas. The gas-liquid reactor in the sense of the invention is defined by a shell, which may be made of, for example, steel or glass, and forms a space therein that can be filled with process liquid at different fill levels. In particular, its use in disposable reactors made of plastics such as PP, PC, PET, LDPE, EVA, PVDC, and composite systems made of these plastics is also advantageous. In addition to the liquid itself, the process liquid may also include other components, such as reactants, suspended cells or organisms, salts, pH adjusters, or other substances. For example, the process liquid may be in the form of an aqueous solution, dispersion, or emulsion. The aeration unit can be connected to a process gas supply line via an inlet. The process gas may be present in a further storage container such as a gas cylinder and delivered in a controlled manner via a control valve. The gas flow rate and gas composition to the aeration unit can be adjusted by a control unit. For example, the transmembrane pressure between the inner membrane of the aeration unit and the process liquid, such as fermentation broth, on the outer membrane can be adjusted via a gas valve. The gas input to the liquid culture medium is typically scaled proportionally to the transmembrane pressure. If the gas flows continuously through / through the inner membrane, the operating mode is set to "crossflow." It is also possible to temporarily overflow the membrane cavity only in the sense of "flushing"; for this, the gas valve is opened simultaneously in "dead-end" operating mode. This is particularly useful if the gas from the process (e.g., CO2 in classic aerobic fermentation) enters the membrane along a concentration gradient and is concentrated there. This concentration leads to a decrease in the overall performance of the gas feed because the partial pressure of the gas to be fed is lower and the driving force is smaller. Furthermore, condensate entering the membrane through the pores can also be discharged in this rapid / intermittent manner. A particularly noteworthy advantage of "dead-end" aeration is that, stoichiometrically, only those gas molecules are "introduced" (i.e., used), and they are also metabolized in the process. This relates to the economic efficiency of the (bio)process. Besides these minimal components, the reactor can, of course, have other internal components. For example, further components such as sensors, feed and discharge lines, heaters, and / or cooling devices can be arranged inside the reactor. Heating or cooling devices can also be arranged outside the reactor.

[0038] In a further preferred embodiment of the gas-liquid reactor, the reactor may not have any other stirring units besides the aeration unit. To achieve a particularly efficient flow distribution, while ensuring homogeneous mixing of the process liquid within the aeration unit, reactors without any further active agitation devices for generating directional flow in the process liquid have proven suitable. In these cases, the process liquid can flow around the hollow fibers in a particularly directional manner, and most of the process gas diffusing from it can be sheared away. Further active agitator units may disrupt the achievable convective symmetry and result in varying gas input per unit volume of process liquid.

[0039] In a further preferred embodiment of the gas-liquid reactor, at least one flow interruptor may be arranged between the reactor shell and the gas receiving chamber. Besides a highly symmetrical convection flow design, it can be useful to redirect convection caused by the gas supply and stirring unit according to the invention by means of flow interruptors in certain areas of the reactor. This can help to better accommodate specific reactor geometries. The flow interruptor may be located between the aeration unit and the reactor wall, and between the aeration unit and the reactor bottom and cover. Particularly preferably, at least one flow interruptor may be installed between the gas supply unit and the reactor cover. Such a flow interruptor may also be disc-shaped. This flow interruptor helps to prevent uncontrolled absorption of gas from the top gas space of the reactor, especially in the case of high exchange area and high circulation rate of the aeration unit. In particular, it effectively prevents the process liquid from conical ingress in the direction of the aeration unit. Preferably, the disc-shaped flow interruptor may be introduced at a height greater than or equal to ¼ and less than or equal to ¾ of the distance from the top edge of the aeration unit to the liquid level.

[0040] The invention further provides the use of the gas-liquid reactor according to the invention for supplying process gases to biological cultures suspended in the process solution or adhered to the interior of the reactor or to the aeration unit. Biological cultures, such as bacteria or fungi, can in principle reproduce in the bioreactor in two different ways. First, the organisms can be in solution, for example, in the form of a suspension, or they can adhere to a surface. Cultivation as a biofilm can in principle take place on the reactor walls or on the aeration unit according to the invention. According to the invention, the latter is preferred because a more uniform nutrient supply can be ensured under dynamic aeration and stirring conditions. In this respect, higher yields and faster conversions can be achieved. The reactor design according to the invention has proven particularly suitable for the reproduction of microorganisms in aqueous fermentation media. The reactor design according to the invention allows for the introduction of targeted and repeatable amounts of suitable gases into the reaction medium, with only a very small portion of the mixing of the entire reactor volume impeded by the aeration unit. There are no dead zones with less mixing, and the process gas requirements (e.g., oxygen) can be uniformly and rapidly distributed throughout the entire process liquid volume. Microorganisms are living organisms that can reproduce within the reactor. Further advantages of the method according to the invention are specifically mentioned in relation to the advantages of the inflation unit according to the invention.

[0041] The invention further provides the use of a gas-liquid reactor for supplying oxygen to bacteria in nutrient media. Specifically, the reactor according to the invention can be used to supply oxygen to bacteria in nutrient media. Bacteria exhibit varying process gas requirements depending on their growth stage in the nutrient medium. In these cases, uniform dispersion and distribution of the introduced oxygen are particularly difficult because the aeration system must have sufficient reserves to selectively introduce small and large amounts of oxygen into the nutrient medium. In these cases, for example, transmembrane pressure must be highly flexible so that small amounts can be repeatedly introduced and large amounts can be introduced without generating bubbles. An example of bacteria that can be used is *Pseudomonas putida*, a Gram-negative rod-shaped bacterium found in water, soil, or plants. In Germany, the laboratory strain *P. putida* KT2440 is classified as an S1 organism and has GRAS status. *P. putida* KT2440 is a very interesting organism for industrial biotechnology because of its diverse metabolism and remarkable tolerance to organic solvents. Furthermore, *P. putida* is a popular heterologous gene expression organism and exhibits a high growth rate on glucose.

[0042] In a more preferred application, biological cultures are suitable for producing foam-forming substances. Foam-forming substances, especially biosurfactants, are particularly difficult to ferment in conventional reactors because these surfactants naturally contribute to particularly strong foam formation. An example of a biosurfactant is rhamnolipid, a surface-active molecule produced by a biocatalyst. These biosurfactants have ecological advantages; unlike petroleum-based surfactants, they can be rapidly bio-metabolized and are therefore more environmentally friendly. These can be produced particularly advantageously in reactors according to the invention, equipped with an aeration unit according to the invention. Other biosurfactants produced by various microorganisms exist. These include sophorolipids produced by yeast. Sophorolipids belong to the glycolipid class. Furthermore, there are biosurfactants belonging to the lipopeptide class, such as surfactantin produced by Bacillus subtilis. Surfactin is primarily used in the medical field. Using the aeration unit of the invention to produce these can result in very little or no foam.

[0043] In a preferred embodiment of the application, the membrane area of ​​the diffusion membrane relative to the reactor packing volume is expressed in cm². 2 Membrane area divided by cm 3 The reactor packing volume can be greater than or equal to 0.05 cm³. -1 And less than or equal to 1.0 cm -1 The membrane area to reactor volume ratio described above has proven particularly advantageous, especially for cell culture and biomolecule synthesis in bioreactors. This ratio allows for the supply of sufficient process gas at different growth stages with significantly varying amounts of biomass, thus providing full controllability of the process gas input at the onset of cell proliferation. This design enables the supply of highly controllable amounts of process gas as needed, and, when the transmembrane bridge is sufficiently small, the appropriate amount can be supplied in subsequent growth stages. Attached Figure Description

[0044] Further advantages and advantageous embodiments of the invention are illustrated by the accompanying drawings and explained in the following examples. It should be noted that the drawings are merely descriptive and are not intended to limit the invention in any way.

[0045] The attached diagram shows:

[0046] Figure 1 A top view of an embodiment of the gas receiving chamber according to the present invention;

[0047] Figure 2 A top view of a further embodiment of the gas receiving chamber according to the present invention;

[0048] Figure 3A side view of an embodiment of the inflation unit according to the present invention;

[0049] Figure 4 A front view of an embodiment of the inflation unit according to the present invention;

[0050] Figure 5 A schematic cross-sectional view of the inflation unit according to the present invention;

[0051] Figure 6 A cross-sectional view of the inflation unit according to the present invention;

[0052] Figure 7 A schematic cross-sectional view of the reactor of the aeration unit according to the present invention;

[0053] Figure 8 A schematic front view of a reactor having an aeration unit according to the invention, including possible convective flow distributions;

[0054] Figure 9 A schematic front view of an inflation unit comprising two inflatable units connected in series according to the present invention;

[0055] Figure 10 A schematic side view of an inflatable unit comprising two inflatable units connected in series according to the present invention;

[0056] Figure 11 This is a schematic front view of an inflation unit according to the present invention, which includes two tandem inflation units having a medium supply.

[0057] Figure 12 A schematic front view of a reactor according to the invention having two in series aeration units with media supply according to the invention;

[0058] Figure 13 A schematic front view of a reactor according to the invention having two aeration units connected in series according to the invention, including possible convective flow distributions;

[0059] Figure 14 A schematic exploded view of the inflation unit according to the present invention. Detailed Implementation

[0060] Figure 1A schematic top view of a gas receiving chamber 1 is shown. The gas receiving chamber 1 is cylindrical and divided into an internal region comprising a container for process gas 4 and / or a container for shaft 4. Through this container 4, the gas receiving chamber 1 is supplied with process gas and mechanical drive energy. The process gas is guided from container 4 through a trapezoidal connector 5 into the actual gas receiving chamber 1. The gas receiving chamber 1 shows a closed surface 2, which has corresponding recesses 3 for receiving a diffusion membrane (not shown). A diffusion membrane in the form of hollow fibers can be sandwiched or glued into the recesses 3, and the diffusion membrane extends into the interior of the gas receiving chamber 1, thereby forming a continuous gas path from container 4 through connector 5 into the actual interior of the gas receiving chamber 1 up to the hollow fiber membrane. The recesses 3 can also be referred to as diffusion membrane fixing surfaces 3. The geometry of the diffusion membrane fixing surfaces 3 determines the planar configuration of the diffusion membrane. In this embodiment, the diffusion membrane fixing surfaces 3 have an arcuate configuration, so the hollow fibers fixed in these recesses generally have the same arcuate membrane surface. The upper and lower gas receiving chambers 1 may have a mirror-image configuration. However, one of the two gas receiving chambers 1 may also lack a container for further process equipment. During operation, the gas receiving chamber 1 can be protected from direct entry of process media by a cover on its lower or upper side.

[0061] Figure 2 It shows the relationship with Figure 1 The arrangement is essentially the same, featuring a gas receiving chamber 2 with a surface, a diffusion film fixing device 3, a receiving device for process gas and / or shaft 4, and a connecting piece 5 between the gas receiving chamber and the gas receiving device 4. Figure 1 Conversely, this point shows that individual cylindrical hollow fibers are inserted into the diffusion membrane fixing surface 3. Therefore, it is clear at this point that this surface is not a continuous, flat membrane, but rather formed by a number of individual hollow fibers offset from each other in the X and Y directions, thus following the arcuate structure of the diffusion membrane fixing surface 3. In this respect, the arcuate geometry of the diffusion membrane is produced. In addition to fixing the hollow fibers in the two gas receiving chambers 1, the individual hollow fibers can also be mechanically fixed to each other (not shown in the figure). This additional fixing can be achieved, for example, by fibers woven into or inserted into the membrane perpendicular to the axis of symmetry of the hollow fibers. Thus, a mesh of hollow fibers and additionally fixed fibers is formed, which can be adjusted to the necessary mechanical load-bearing capacity of the diffusion membrane, as a function of the number of further fixing points and the mechanical properties of the additional fibers.

[0062] Figure 3An embodiment of the gas supply unit 10 according to the invention is shown. The entire gas supply unit 10 can be seen in this figure. Process media, process gas, and energy are supplied to the gas supply unit 10 via supply lines 9. The supply lines lead to a container 4 (not shown) for the gas supply / shaft of the first gas receiving chamber 1. The gas receiving chamber 1 is then provided with a top cover. Extending from the gas receiving chamber 1 are individual diffusion membranes 6, which generally extend from the first gas receiving chamber 1 (shown at the top here) to the lower gas receiving chamber 1. The planar design of the diffusion membranes 6, achieved by a specific arrangement of hollow fibers, can be seen in particular in this figure. The diffusion membranes 6 extend from the first gas receiving chamber 1 to the second gas receiving chamber 1 and are held in a central position by a holding disc 7. Therefore, gas conduction of the individual diffusion membranes 6 is not interrupted between the gas receiving chambers 1. The diffusion membranes 6 can be held solely by the holding disc 7, deviating from their original position or mechanically tensioned. Thus, the holding disc 7 can change the orientation of the individual diffusion membranes 6, which, of course, affects the achievable convection of the gas filling unit 10. The figure also shows a flow interruptor 8, which is arranged above the aeration unit 10 along the direction of the reactor top space. This flow interruptor 8 is optional and can prevent the formation of eddies in the reactor liquid, especially at the very high rotational speed of the aeration unit 10. This can help to further reduce bubble formation.

[0063] Figure 4 A front view of the gas supply unit 10 according to the invention is shown. Process media (process gas) and mechanical energy are supplied to the gas supply unit 10 via supply lines 9. The supply lines lead to a gas supply / shaft container (not shown) for the first gas receiving chamber 1. Individual diffusion membranes 6 extend from the gas receiving chamber 1, generally extending from the upper gas receiving chamber 1 to the lower gas receiving chamber 1. The diffusion membranes 6 extend from the first gas receiving chamber 1 to the second gas receiving chamber 1 and are held in a centrally located position by a holding plate 7. A flow circuit breaker 8 is also shown in this figure, arranged above the gas supply unit 10 along the direction of the reactor top space.

[0064] Figure 5An example of media feeding within a gas supply unit 10 according to the invention is shown. The gas supply unit 10 is driven by a hollow shaft 9 connected to a gas receiving chamber 1 at a container 4 for gas supply / shaft. The shaft transmits mechanical energy and process gas to the gas receiving chamber 1. Gas is introduced into an internal gas container 11 through the container 4 for gas supply and an internal gas container connected to the gas container. A separate hollow fiber membrane 6 is arranged on the gas receiving chamber 1 to extend into the internal gas receiving chamber 11. Process gas is thus supplied to the hollow fiber membrane through the internal gas receiving chamber 11, the process gas being introduced into the gas receiving chamber 1 through the hollow fibers of the diffusion membrane 6. The process gas can enter the process liquid from the hollow fibers of the diffusion membrane 6, thereby supplying process gas to the liquid. The two gas receiving chambers 1 are thus additionally interconnected by a mechanical support 12. This support can be used for other technical functions in addition to purely mechanical support. In this embodiment, the second (lower) gas receiving chamber 1 also includes a container 4 for process gas. Process gases that do not diffuse from membrane 6 are guided out of inflation unit 10 via a hollow shaft support 12. Therefore, inflation unit 10 operates in a "lateral flow" mode. Typically, process gases can be supplied and discharged through a central hollow shaft 12, which also serves as a mechanical support. In particular, the latter design reduces the number of necessary connection points.

[0065] and Figure 5 Same, Figure 6 The flow of media within a gas supply unit 10 according to the invention is illustrated. The gas supply unit 10 is supplied with process gas and / or mechanical energy by a container 4. The container 4 is connected to a gas receiving chamber 1, whereby the process gas is supplied to an inner gas receiving chamber 11. A separate hollow fiber membrane 6 is disposed on and extends into the gas receiving chamber 1. Thus, process gas is supplied to the hollow fiber membrane 6 through the inner gas receiving chamber 11, and this process gas is introduced into the other gas receiving chamber 1 through the hollow fibers of the diffusion membrane 6. The process gas can enter the process liquid from the hollow fibers of the diffusion membrane 6, thereby supplying process gas to the liquid. The two gas receiving chambers 1 are further interconnected by a mechanical support 12, which optionally also guides the process gas. In this embodiment, the second (lower) gas receiving chamber 1 also includes the container 4 for the process gas. Process gas that does not diffuse from the membrane 6 is guided out of the inflation unit 10 via a gas line in the mechanical support 12. In this embodiment, the inflation unit 10 can operate in a "lateral flow" mode. Therefore, the supply and discharge of process gases are typically achieved via a central mechanical support 12 in the form of a hollow shaft. In particular, the latter design reduces the number of necessary connection points.

[0066] Figure 7A bioreactor 20 according to the invention is shown, in which an aeration unit 10 is located. The reactor 20 is filled with a process liquid, which is present in the reactor 20 up to the process liquid level 21. The aeration unit 10 is held in the reactor 20 and moves within the reactor 20 by a process gas / mechanical energy supply in the form of a hollow shaft 9. Further configuration of the aeration unit 10 can be derived from... Figure 5 As described in the figure. Further flow interruptors or conductors 8 may also be arranged on the reactor wall 22 or in the liquid volume of the reactor 20 (not shown in the figure), thereby the convection of the process liquid can be affected by the further flow interruptors 8.

[0067] Figure 8 A possible design for a reactor 20 according to the invention, having an aeration unit 10 according to the invention, is shown. The figure illustrates a possibility of forming convective flow within the reactor 20. The convective flow is generated by a simulation of the flow behavior as a function of the geometry of the reactor 20 and the aeration unit 10. In the figure, it can be seen that the aeration unit 10 results in very symmetrical convection, thereby actively circulating the process liquid, particularly within the aeration unit 10. Specifically, the latter can facilitate the particularly efficient introduction of process gas into the process liquid through the diffusion membrane 6. In particular, the convection of the process liquid around the individual hollow fibers 6 forms small bubbles, which are sheared off from the surface of the hollow fibers 6 and thus can supply process gas to the process liquid. This also ensures that the bubble size on the hollow fiber surface remains small.

[0068] Figure 9 shows a series-connected aeration unit 30 consisting of two separate aeration units 10 coupled via a modular connector 31. Through the modular connector 31, process gas and mechanical motion are transferred from the upper aeration unit 10 to the lower aeration unit 10. By interconnecting several aeration units 10, process gas can be supplied very efficiently for different reactor geometries and sizes. The result is a design with minimal connections and reliable, predictable convection flow. This means that it can be easily scaled up to larger reactors 20, especially via the series-connected gas supply units 30.

[0069] Figure 10 It shows from another perspective Figure 9 The implementation plan.

[0070] Figure 11An example of media supply in an arrangement of two gas supply units 10 connected in series is shown. The gas supply unit 10 is driven by a hollow shaft 9, which is connected to a gas receiving chamber 1 at a gas supply / shaft container 4. Gas is supplied to the other gas receiving chamber 1 through a separate hollow fiber membrane 6 via the gas supply container 4 and an inner cavity gas container 5 connecting the gas container. From this second gas receiving chamber 1, the remaining process gas can enter the second gas supply unit 10 through a modular connector 31. The modular connector 31 between the two gas supply units 10 enables the transfer of process gas and mechanical drive energy between the respective gas supply units 10.

[0071] Figure 12 An embodiment of the reactor 20 according to the invention is shown, having two series-connected gas supply units 30, which consist of two separate gas supply units 10. Process gases can also be reliably supplied, particularly to reactors 20 with a large aspect ratio, by connecting several gas supply units 10 in series.

[0072] Figure 13 The possible flow distribution of a reactor 20 equipped with two aeration units 30 connected in series is shown. The result is uniform convection of the process liquid throughout the reactor area and within the series-connected aeration units 30.

[0073] Figure 14An exploded view of the gas supply unit 10 according to the invention is shown. For example, the gas supply unit 10 can be driven and supplied with process gas via a hollow shaft (not shown) connected to the gas receiving chamber 1 at the container 4. The shaft provides mechanical power to the unit and delivers the process gas to the gas receiving chamber 1. Individual hollow fiber membranes 6 are arranged on the gas receiving chamber 1 such that they extend into the inner gas receiving chamber 11. Process gas is thus supplied to the hollow fiber membranes through the inner gas receiving chamber 11, and the process gas is introduced into the other (lower) gas receiving chamber 1 through the hollow fibers of the diffusion membrane 6. The process gas can enter the process liquid from the hollow fibers of the diffusion membrane 6, thereby supplying process gas to the liquid. The two gas receiving chambers 1 are thus additionally interconnected by a mechanical support 12. This support 12 can be used for other technical functions besides purely mechanical support. In this embodiment, the second (lower) gas receiving chamber 1 also includes the container 4 for the process gas. Process gas that has not diffused from the membrane 6 is again led out of the gas supply unit 10 via the hollow shaft of the mechanical support 12. In this embodiment, the inflation unit 10 therefore operates in a "lateral flow" mode. Typically, the process gas can be supplied or discharged through a central hollow shaft in a mechanical support 12, which is connected to the outer edge of one or both of the two gas receiving chambers 1 via a container 4. In particular, the latter embodiment reduces the number of necessary connection points and contributes to a compact design. Additionally, as can be seen in this embodiment, each gas receiving chamber 1 can be protected from above and below by a cover plate.

[0074] Reference Marker

[0075] 1 Gas receiving chamber

[0076] 2 Surface area gas receiving chamber

[0077] 3. Diffusion film fixing surface

[0078] 4. Containers for gas supply / shaft

[0079] 5. Connect to the inside of the gas inlet - gas inlet

[0080] 6. Diffusion membrane

[0081] 7. Hold the plate

[0082] 8. Mobile circuit breakers

[0083] 9. Process gas / mechanical energy supply

[0084] 10 inflation units

[0085] 11 Internal Gas Receiving Chamber

[0086] 12 Support components

[0087] 20 Gas-Liquid Reactors

[0088] 21 Process liquid level

[0089] 22 Reactor shell

[0090] 30 inflation units arranged in series

[0091] 31 Module Connector

Claims

1. An aeration unit for introducing process gas into a liquid located in a reactor without bubbles, characterized in that, The inflation unit includes at least: - A first gas receiving chamber and a second gas receiving chamber spaced apart therefrom for receiving process gases, the two gas receiving chambers being connected to each other by at least two two-dimensional, gas-conducting diffusion membranes comprising hollow fibers spaced apart from each other and at least partially fixed to each other; - A container for gas supply on at least one of the gas receiving chambers; - A container for the shaft on at least one of the gas receiving chambers; The aeration unit for aerating the liquid in the reactor can supply process gas through the gas supply container, can be configured to rotate through the container for the shaft, and can form convective flow in the reactor through the rotational movement of the aeration unit in the liquid.

2. The inflation unit according to claim 1, wherein, The projection of the diffusion membrane onto the gas receiving chamber has an arc geometry.

3. The inflation unit according to claim 1, wherein, The container for the gas supply and the container for the shaft are arranged on only one gas receiving chamber.

4. The inflation unit according to claim 1, wherein, The two gas receiving chambers are each cylindrical and are connected to each other by one or more mechanical supports.

5. The inflation unit according to claim 4, wherein, At least one retaining disc is disposed between the two gas receiving chambers on the mechanical support, which is configured to mechanically retain the diffusion membrane.

6. The inflation unit according to claim 4, wherein, The mechanical support is adapted to deliver process gas from the gas receiving chamber.

7. The inflation unit according to claim 1, wherein, The ratio of the total cross-sectional area of ​​the hollow fiber to the cross-sectional area of ​​the gas receiving chamber is greater than or equal to 5% and less than or equal to 45%.

8. The inflation unit according to claim 1, wherein, The filling density of the diffusion membrane relative to the volume of the air-filling unit, expressed as the surface area of ​​the hollow fiber divided by the volume of the air-filling unit, is greater than or equal to 0.1 cm³. -1 And less than or equal to 7.5 cm -1 .

9. A method for aerating a process liquid within a reactor, characterized in that, The gas input is achieved by the inflation unit according to any one of claims 1-8.

10. The method according to claim 9, wherein the rotational speed of the membrane surface at the outermost edge of the inflation unit is greater than or equal to 0.1 m / s and less than or equal to 5 m / s.

11. A gas-liquid reactor, comprising at least a reactor shell, a drive unit, a gas supplier, and an aeration unit according to any one of claims 1-8.

12. The gas-liquid reactor according to claim 11, wherein, The reactor does not include a stirring unit other than the aeration unit.

13. The gas-liquid reactor according to claim 12, wherein, At least one flow circuit breaker is arranged between the reactor shell and the gas receiving chamber.

14. Use of the gas-liquid reactor according to claim 11, for supplying process gas to biological cultures suspended in a process solution or adhered to the interior of the reactor or the aeration unit.

15. The use according to claim 14, wherein the biological culture is adapted to produce a foam-forming substance.

Images