Field of invention

The present invention relates to an aeration system and more particularly it relates to an improved aeration system for bioreactor, fermenter and process vessel which is capable to reduce air-bubbles size for even distribution of air-gas mixture to increase the oxygen transfer rate and mass transfer rate for enhancing the cell growth rate as well as microbial growth rate.

Background of invention Bioreactors are commonly cylindrical shaped vessels/tanks which are manufactured or designed to carry out a biochemical process involving microorganisms and biochemically active substances derived from such microorganisms. The bioreactors are usually used for providing a controlled environment for the growth of biological cultures i.e. cells, bacteria, yeasts or fungi. The said cultures are used to produce a variety of biologically active substances, including pharmaceuticals, fragrances, fuel and the like. The aeration systems play vital role in disposable as well as non-disposable bioreactors and stainless steel bioreactors to reduce the air-bubbles size for even distribution of air-gas mixture to increase the oxygen transfer rate for enhancing the cell growth rate as well as microbial growth rate.

Provision of an oxygen supply is a key factor in cellular metabolic processes in bioreactors. Although animal cell cultures consume substantially less oxygen than bacteria and yeast cultures, ensuring an efficient supply is the greatest challenge facing the operation of a cell culture bioreactor. In addition to supplying the cells with oxygen, the concentration of dissolved carbon dioxide also plays a part as a controlled variable.

The pharmaceutical industry utilizes numerous aeration systems in stainless steel tanks of bioreactors for supplying oxygen in order to develop animal and human cell cultures which require higher energy consumption which results in increased maintenance and operational cost. Conventional bioreactors are designed as stationary pressurized vessels which utilizes an aeration system for increasing the mass transfer rates and oxygen transfer rate. The main problem involved in conventional aeration system is the increased air-gas bubbles size which causes heterogeneous mixing of the microorganisms which results in decreasing the oxygen transfer rate and mass transfer rate and which is the reason of decreased cell growth rate and decreased microbial growth rate. The microorganisms includes all bacteria, archaea, most protozoa, microalgae, cyanobacteria, fungi, algae, animal and human cell cultures and some micro-animals such as rotifers as etc.

There are two conventional aeration methods: aerating the headspace of the bioreactor and direct injection of the gases through aeration tubes or rings. For this purpose, use is made not only of the aeration rings known from fermenter with bores or gas outlet openings of for example 0.8 mm but also of "microspargers" made from sintered plastics with pore sizes of for example 20 to 45 pm, which likewise form gas outlet openings. Both kinds have specific advantages and drawbacks.

The aeration ring produces larger bubbles, which means that higher gas throughput rates are required to achieve the same "oxygen transfer rate". With its relatively large bubbles, the ring sparger is suitable for stripping or sweeping out CO2 with air, for example. With its relatively small bubbles, the micro sparger is particularly suitable for supplying oxygen. One drawback, however, is that under unfavorable conditions foaming may occur due to the relatively extra smaller bubbles.

The aeration system of the bioreactors may include a hollow tube or circular disc having porous holes or pores for diffusing and dispersing the air/gas into the stirred tank which is not efficient for producing an adequate aerating effect for increasing the cell growth rate and microbial growth rate. Further, an efficient aerating effect can not be achieved due to imprecise porous holes/pores in the conventional aeration device. Hence, the aeration systems for bioreactors are being progressively viewed as serious alternatives from the performance and an economical point of view.

One such aeration device has been disclosed in US 2013/0175716 in which the aeration element with gas outlet openings arranged in housing, and the aeration element taking the position of a micro sparger; and the gas outlet openings of which are spaced apart from one another and have a size of between lOOpm and 200pm. But, the prior art disclosure neither discloses nor teaches the required angle of the gas outlet openings for increasing the aerating effect. Hence, the problems associated with the prior art is that the gas outlet openings are located randomly and due to that the aeration device cannot generate an adequate air-gas bubbles flow of prerequisite sizes and aerating effect to cause homogenous O2/C02 gas mixing to increase the gas to liquid transfer rate into the bioreactor.

The absolute necessity for an improved aeration system is a real constraint that causing an aerating effect in bioreactors is a basic necessity for diffusing and dispersing the air-gas bubbles into the bioreactor to increase the oxygen transfer rate as well mass transfer rate. Thus, the aeration devices/systems for bioreactors of the current state of art are less efficient, especially when it comes to oxygenating and aerating. Though, the presently available aeration devices provide numerous advantages, there is still scope for auxiliary improvement to the existing aeration devices for bioreactors and fermenters.

Hence, it is essentially needed to provide an improved aeration system that is an efficient in terms of diffusion and dispersion of air-gas bubbles into the bioreactors for increasing the gas to liquid transfer rate and thereby increasing the oxygen transfer rate and mass transfer rate to enhance the microbial growth rate as well as cell growth rate. Objects of Invention

The main object of the present invention is to provide an improved aeration system for bioreactor, fermenter and process vessel. Another object of the present invention is to provide an improved aeration system for bioreactor, fermenter and process vessel which generates and maintain an adequate air-gas bubbles flow of prerequisite sizes to cause homogenous O2/C02 gas mixing to increase the gas to liquid transfer rate into the bioreactor.

Further, another object of the present invention is to provide an improved aeration system for bioreactor, fermenter and process vessel which is an efficient in terms of diffusion and dispersion of air-gas mixture into the bioreactor for increasing the oxygen transfer rate and mass transfer rate. Still, another object of the present invention is to provide an improved aeration system for bioreactor, fermenter and process vessel which will enhance the cell growth rate as well as microbial growth rate. Yet, another object of the present invention is to provide an improved aeration system for bioreactor, fermenter and process vessel which prevents the foaming in unfavorable conditions of the bioreactors. Yet, another object of the present invention is to provide an improved aeration system for bioreactor, fermenter and process vessel which increases the overall efficiency of the aeration system in terms of generating the aerating effect into the bioreactor. Yet, another object of the present invention is to provide an improved aeration system for bioreactor, fermenter and process vessel which reduces the risk of cross contamination and enhances the biological and process safety of the bioreactor.

Yet, another object of the present invention is to overcome one or more drawbacks and shortcomings of the prior art bioreactor, fermenter and process vessel or to at least provide a useful alternative.

Brief description of drawings

Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the present embodiment when taken in conjunction with the accompanying drawings.

Fig. 1 illustrates a schematic perspective view of an improved aeration system for bioreactor, fermenter and process vessel according to the present invention. Fig. 2 illustrates a schematic perspective view of an improved aeration system with the direction of an air-gas bubbles flow diffusing at predefined angle from the sparger ring according to the present invention. Summary of invention

The present invention relates to an improved aeration system being disposed into a bioreactor, fermenter or process-vessel, said vessel comprises an inlet pipe and an agitator shaft configured with impellers being centrally and vertically extended into the vessel, comprising a sparger ring connected to the inlet pipe is concentrically disposed within the vessel. The agitator shaft configured with impeller is extended through the center of the sparger ring. The impeller comprises impeller blades circumferentially radially fixed to an impeller disc which is rotatably mounted to the agitator shaft through an impeller hub. The sparger ring is provided with plurality of pores disposed at an inner peripheral surface at angle of 35° with respect to plane of the ring to allow bubbles flow to be diffused from the pores and directed first towards the impeller hub to reduce the bubbles size and then redirected towards the impeller blades for even distribution of air-gas mixture and to reduce the risk of damage to impeller.

Detailed description of invention

The nature of the invention and the manner in which it works is clearly described in the complete specification. The invention has various embodiments and they are clearly described in the following pages of the complete specification. Before explaining the present invention, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and not of limitation. The present invention discloses an improved aeration system for delivering and diffusing controlled volume of air to a growth media containing vessel like bioreactor, fermenter etc. Such aeration system is used in bioreactors where it is necessary to control the oxygen content and other properties, of the growth media to facilitate proper growth of cells and microorganisms. However, the aeration systems can also be used in fermentation systems and in other fluid processing systems where it is needed or desirable to expose a gas to a fluid.

Before explaining the present invention, it is assumed that the present aeration system is housed and accommodated within the bioreactor/fermenter vessel which is not shown in figure. Further, the bioreactors and fermenters are of any conventional types. However, for sake of convenience, only necessary components i.e. agitator shaft, impellers, sparger ring and inlet pipe are referred in the present invention.

The term "impeller" in the present invention refers to a device that is used for agitating or mixing the contents of a bioreactor. The impeller may agitate the fluidic medium by stirring or other mechanical motion. The impeller of the instant invention includes, but is not limited to, a rushton, a marine, a hydrofoil, a pitch type blade, dispersion blade and any other commercially available impeller.

The exemplary embodiment of the present invention is shown in

Fig. 1. Now as shown in Fig.l, the improved aeration system (1) according to the present invention for bioreactor, fermenter and process vessel (not shown in figure) comprises a sparger ring (2) made of SS tubular pipe being concentrically disposed and accommodated within the bioreactor (not shown in figure) in such manner that an agitator shaft (4) provided with impeller (3) is extended through the centre of the sparger ring (2). Said sparger ring (2) is supplied with air by an inlet pipe (5) being joined to the sparger ring (2). Said inlet pipe (5) is vertically extended from the top of the bioreactor/fermenter and may be connected to an air filter bag (not shown in figure). Further, the impeller (3) comprises impeller blades (3a) circumferentially radially fixed to an impeller disc (3b) which is rotatably mounted to the agitator shaft (4) through an impeller hub (3c). The ratio of outer diameter (OD) of the impeller (3) to the internal diameter (ID) of the vessel is preferably kept in the range of 0.25-0.45. Further, the ratio of diameter of the impeller disc (3b) to the outer diameter (OD) of the impeller (3) is 0.50-0.60 and the ratio of outer diameter (OD) of the sparger ring (2) to the diameter of the impeller disc (3b) is 1.20-1.65.

Hence due to the ratio of 0.25-0.45, the outer diameter (OD) of the impeller (3) is 0.25-0.45 times the internal diameter (ID) of the vessel. Further due to the ratio of 0.5-0.6, the diameter of the impeller disc (3b) is 0.5-0.6 times the outer diameter (OD) of the impeller (3); and due to the ratio of 1.20-1.65, the outer diameter (OD) of the sparger ring (2) is 1.20-1.65 times the diameter of the impeller disc (3b).

Though, in the present exemplary embodiment, the sparger ring is shown in circular shape, however it may be of any other shapes i.e. elliptical or oval. Referring continuous with Fig. 1, said sparger ring (2) according to the present invention is provided with a plurality of pores (2a) disposed at an inner peripheral surface of the sparger ring (2). The air supplied by the inlet pipe (5) emerges from the sparger ring (2) through said pores (2a) in the form of an air-gas bubbles flow (6). Each of said pores (2a) is formed at an angle, preferably of 35° with respect to the plane of the sparger ring (2) so that an air-gas bubbles flow (6) to be diffused from the pores (2a) is directed towards the impeller hub (3c) to reduce the air gas bubbles size. The air-gas bubbles flow (6) diffusing from the pores (2a) of the sparger ring (2) is shown in Fig. 2.

As shown in Fig. 2, said emerged air-gas bubbles flow (6) is directed towards and impinged at the impeller hub (3c) which substantially reduces the air bubble size. Thereafter, the air-gas bubbles flow (6) is redirected towards the impeller blades (3a) for homogeneous O2/CO2 gas mixing and even distribution of the air-gas mixture to reduce the risk of damage to the impellers (3), and increases the gas to liquid transfer rate, and thereby increasing the oxygen transfer rate (OTR) and microbial growth rate as well as cell growth rate. Due to an enough aerating effect and even distribution of the air-gas mixture, low shear will reduce chances of damage to cells and increases the cell growth rate and mass gas transfer.

The aeration system of the present invention reduces the risk of the damage to the impellers that substantially increases the overall efficiency of the aeration system in terms of generating the aerating effect within the bioreactor and fermenter; and the diffusion of the air- gas mixture from the pores reduces the bubbles size up-to 80% and more as compared to the conventional ring aeration devices. Further, the said aeration system generates sufficient aerating effect which leads to better O2/CO2 gas mixing and increases the gas to liquid transfer rate. The even distribution of the air-gas mixture results in lower shear which reduces the chances of damage to the cells and increases the cell growth rate microbial growth rate. The present invention is experimented and illustrated more in details in the following example. The example describes and demonstrates embodiments within the scope of the present invention. This example is given solely for the purpose of illustration and is not to be construed as limitations of the present invention, as many variations thereof are possible without departing from spirit and scope.

EXAMPLE 1:

The experiment for measuring the microbial/cell growth rate was carried out in bioreactor/fermenter comprising an aeration system having design and dimensions according to the present invention. The outer diameter (OD) of the impeller (3) was kept 0.35-0.45 times the internal diameter (ID) of the vessel. Further, the diameter of the impeller disc (3b) was kept of 0.5-0.6 times the outer diameter (OD) of the impeller (3) and the outer diameter (OD) of the sparger ring (2) was kept 1.20-1.65 times the diameter of the impeller disc (3b). By using the presently exemplified design of the aeration system in the bioreactor, the following experimental results of the microbial/cell growth rate were obtained.

From aforesaid experimental results, it is observed that by using the aeration system of the present invention, the microbial/cell growth rate is substantially enhanced.

The invention has been explained in relation to specific embodiment. It is inferred that the foregoing description is only illustrative of the present invention and it is not intended that the invention be limited or restrictive thereto. Many other specific embodiments of the present invention will be apparent to one skilled in the art from the foregoing disclosure. All substitution, alterations and modification of the present invention which come within the scope of the following claims are to which the present invention is readily susceptible without departing from the spirit of the invention. The scope of the invention should therefore be determined not with reference to the above description but should be determined with reference to appended claims along with full scope of equivalents to which such claims are entitled.

Reference numerals

• An improved aeration system (1)

• Sparger ring (2)

• Pores (2a)

• Impeller (3)

• Impeller blade (3a)

• Impeller disc (3b)

• Impeller hub (3 c)

• Agitator shaft (4)

• Inlet pipe (5)

• Bubbles flow (6)