Air-lift bioreactor

Abstract

An air-lift bioreactor includes a vessel allowing a culture medium to flow thereinside, and a sparger disposed inside the vessel. The sparger includes a plurality of angle-adjustable nozzles, which may disturb a higher-viscosity culture medium, whereby the culture medium may circulate well inside the vessel.

Description

[0001] AIR-LIFT BIOREACTOR

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a bioreactor, particularly to an air-lift bioreactor.

[0004] DESCRIPTION OF THE PRIOR ART

[0005] In general, bioreactors are used to culture microorganisms, plant cells or animal cells. The most common bioreactors include stirred type bioreactors and air-lift bioreactors. The stirred type bioreactor has a mechanical agitator device (normally blades or turbines) for stirring culture media and biological materials. The advantages of the stirred type bioreactors include mixing the materials well, improving oxygen transfer efficiency and nutrient distribution, and providing a homogeneous fermentation environment. Therefore, the stirred type bioreactors usually applies to high oxygendemanding fermentation processes, such as the processes of culturing yeast, bacteria, and fungi. The air-lift bioreactors use the uprising flow of air or another gas to perform agitation and mixing. The air-lift bioreactors are normally without mechanical stirring devices. The gas is introduced into the air-lift bioreactor from the bottom thereof. The advantages of the air-lift bioreactors include no stirring device, simple structure, and low operation cost. Therefore, the air-lift bioreactors are suitable for large-scale fermentation. Because the air-lift bioreactor is without mechanical stirring, it is friendlier to the cells or microorganisms that are sensitive to shear or cutting. Thus, the air-lift bioreactor usually applies to cell culture, wastewater treatment, and the fermentation of some specified microorganisms. However, while the microorganisms have grown with high density biomass, the viscosity of the culture medium rises so as to affect circulation and mass transfer and degrade the cultivation effect. SUMMARY OF THE INVENTION

[0006] In order to solve the abovementioned problems, the present invention provides an air-lift bioreactor. The air-lift bioreactor free of any blades is equipped with a sparger having direction-adjustable nozzles to achieve a better circulation effect.

[0007] In order to solve the abovementioned problems, an air-lift bioreactor is provided therein to include a sparger having direction-adjustable nozzles to promote the flow of the culture medium, improve mass transfer efficiency, and facilitate the cultivation of filamentous fungi and animal cells.

[0008] The present invention proposes an air-lift bioreactor, which comprises a vessel including a first space providing a culture medium to flow thereinside, and a sparger disposed inside the first space of the vessel. The sparger includes a first connecting pipe having a plurality of via-holes thereon; a second connecting pipe, wherein the second connecting pipe and the first connecting pipe are annular structures and concentrically disposed inside the vessel; a plurality of channels disposed between and connected with the first connecting pipe and the second connecting pipe; a gas pipe having a first terminal extended to the vessel and a second terminal extended to at least one of the first connecting pipe, the second connecting pipe and the channels; and a plurality of nozzles disposed on at least one of the second connecting and the channels, wherein each nozzle has an adjusting tube, and the adjusting tube is used to adjust the angle of the nozzle in the first space.

[0009] The present invention also proposes an air-lift bioreactor, which comprises a vessel including a first space providing a culture medium to flow thereinside; a gas pipe disposed inside the first space and having a first terminal extended to the vessel; and a sparger ring disposed inside the first space and on the gas pipe, and orthogonally connected with the gas pipe. The sparger ring includes a first connecting pipe having a plurality of via-holes thereon; and a plurality of channels disposed between and connected with the first connecting pipe and the gas pipe, wherein the channels have a plurality of nozzles; each nozzle has an adjusting tube, and the adjusting tube is used to adjust the angle of the nozzle in the first space.

[0010] In one embodiment, the adjusting tube includes an arc-shape hollow tube.

[0011] BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Fig.l is a perspective view schematically showing an air-lift bioreactor after assembled, according to a first embodiment of the present invention.

[0013] Fig.2 is a perspective sectional view schematically showing the air-lift bioreactor according to the first embodiment of the present invention.

[0014] Fig.3 is a perspective view schematically showing a portion of air-lift bioreactor according to the first embodiment of the present invention.

[0015] Fig.4 is a perspective view schematically showing a sparger according to the first embodiment of the present invention.

[0016] Fig.5 is a perspective view schematically showing a sparger according to a second embodiment of the present invention.

[0017] Fig.6 is a diagram schematically showing that the sparger disturbs the flow of the culture medium according to one embodiment of the present invention.

[0018] Fig.7 is a perspective sectional view schematically showing an air-lift bioreactor according to a second embodiment of the present invention.

[0019] Fig.8 is a perspective sectional view schematically showing an air-lift bioreactor according to a third embodiment of the present invention.

[0020] DESCRIPTION OF THE PREFERRED EMBODIMENT

[0021] Fig.l is a perspective view schematically showing an air-lift bioreactor after assembled, according to a first embodiment of the present invention. Fig.2 is a perspective sectional view schematically showing the air-lift bioreactor according to the first embodiment of the present invention. Fig.3 is a perspective view schematically showing a portion of the air-lift bioreactor according to the first embodiment of the present invention. Refer to Figs.1-3. The air-lift bioreactor 1 of the present invention includes a vessel 10, an upper lid 12 and a sparger 30. The vessel 10 provides a first space 11 for receiving a culture medium 13. The upper lid 12 is disposed on an open end of the vessel 10 and may be fixed to the vessel 10 to seal the first space 11 in an appropriate method. A water jacket 14 encases the whole or partial outer sidewall of the vessel 10. The water jacket 14 may include an annular heating element to heat the vessel 10 or an annular cooler pipe to regulate the temperature of the vessel 10. Several coupling ends may be deposited on the bottom of the vessel 10 (such as a first coupling end 16), whereby to connect with external devices / apparatuses or output / input materials. Several controlling / indi eating parts 18 deposited on the outer sidewall of the vessel 10 may be configured to electrically control or indicate the parameters of the fermentation process of the air-lift bioreactor 1. The air-lift bioreactor 1 may further include one or more stands 19 for supporting the vessel 10. It is understood: the upper lid 12 may also have several coupling ends for connecting with external devices / apparatuses or outputting / inputting materials.

[0022] Refer to Figs.1 -3 again. The sparger 30 is disposed inside the first space 11 of the vessel 10. The sparger 30 includes at least one first gas pipe 32, a second gas pipe 34, one or more first connecting pipes 36, one or more second connecting pipes 26, the channels 38, and a plurality of nozzles 22. The first connecting pipe 36, the second connecting pipe 26, the channels 38, and the nozzles 22 jointly form a sparger ring. The first gas pipe 32 and the second gas pipe 34 are generally a long strip respectively and have respective a first terminal 31 disposed on the upper lid 12 to connect with an external pumping device / apparatus (not shown in the drawings). The first gas pipe 32 and the second gas pipe 34 also respectively has a second terminal 35 to connect with the first connecting pipe 36 and the channel 38. The first gas pipe 32 and the second gas pipe 34 are essentially parallel to each other and essentially orthogonal to the first connecting pipes 36, the second connecting pipes 26, and the channels 38. The plurality of first connecting pipes 36 and the plurality of second connecting pipes 26 may be of annular shape with different ring radii. The first connecting pipes 36 and the second connecting pipes 26, which respectively have different ring radii, are concentrically disposed near the bottom of the vessel 10. The plurality of channels 38 may be of a straight pipe. Some channels 38 are disposed between and connected with the first connecting pipes 36 respectively having different ring radii. The other channels 38 are disposed between and connected with the first connecting pipes 36 and the second connecting pipes 26. These channels 38 enables the first connecting pipes 36 and the second connecting pipes 26 interconnect each other. Furthermore, the first gas pipe 32 and the second gas pipe 34 may be connected to different positions of the same first connecting pipe 36, or connected to the first connecting pipes 36 respectively having different radii, or connected to related positions of the second connecting pipe 26. For example on the related positions, the first gas pipe 32 and the second gas pipe 34 are separated by 180 degrees and respectively connected with the first connecting pipes 36 or the second connecting pipe 26. However, the present invention does not limit to the abovementioned positions of the first gas pipe 32 and the second gas pipe 34. Another channels 38 may be connected with the nozzles 22 and disposed between and connected with the nozzles 22 and the first connecting pipes 36. Optionally, some the channels 38 are disposed between and connected with the first connecting pipes 36 and the second connecting pipes 26. In the first embodiment, with the channels 38, the nozzles 22 are connected to the second connecting pipe 26 having the smallest ring radius. However, it is not limited to. To describe it in further detail, each nozzle 22 is connected with the corresponding second connecting pipe 26 through the adjusting tube 24. The adjusting tube 24 is an arc-shape tube used to adjust the direction of the corresponding nozzle 22.

[0023] Fig.4 is a perspective view schematically showing a sparger according to the first embodiment of the present invention. Fig.5 is a perspective view schematically showing a sparger according to a second embodiment of the present invention. Refer to Fig.4 and Fig.5 for further demonstration of the present invention. There are via-holes 33 on each of the first connecting pipes 36 and interconnecting with the hollow pipe body of the corresponding first connecting pipe 36. While gas is transferred to the first connecting pipe 36 from the first gas pipe 32 or the second gas pipe 34, the gas will be distributed out to the first space of the vessel through the via-holes 33. In the case that the first space is full of a culture medium, the gas through the via-holes 33 will form bubbles in the culture medium, whereby to enhance the oxygen transference and contribute the driving force of recirculation inside the air-lift bioreactor 1. The first connecting pipes 36 may be made of a metallic material, a plastic material, or another appropriate material. In the present invention, the number of the concentric annular rings of the first connecting pipes 36 is not limited to that shown in the drawings. The more the rings of the first connecting pipes have, the larger the area where the via-holes are allowed to form. The via-holes 33 may be regularly or irregularly distributed on the first connecting pipe 36. In the regular distribution, the via-holes 33 may be periodically distributed along the circumference of the first connecting pipe 36 and separated by a given distance. In the irregular distribution, the via-holes 33 are distributed on different regions of the same first connecting pipe 36 in different densities or on different first connecting pipes 36 in different densities. Besides, the via-holes 33 may have different sizes. A smaller viahole forms a smaller bubble.

[0024] Refer to Fig.4 and Fig.5 again. The differences between the second connecting pipe 26 and the first connecting pipe 36 is there is no via-holes on the body of the second connecting pipe 26 having nozzles 22. While the gas is transferred to the second connecting pipe 26 from the first gas pipe 32 or the second gas pipe 34, the gas inside the second connecting pipe 26 is output to the first space of the vessel through the nozzles. When the first space is full of a culture medium, the gas spurted from the nozzles 22 will disturb the culture medium and facilitate the flow of the culture medium inside the first space. It is understood that the bubbles formed by the gas output by the via-holes also facilitate the flow of the culture medium inside the first space too, enhance the oxygen transference and contribute the driving force of recirculation. However, the gas output from the via-holes possibly contributes insufficient transference capability when the culture medium becomes more viscous with increase of fermentation time in the first space.

[0025] Fig.6 is a diagram schematically showing that the sparger disturbs the flow of the culture medium. Refer to Fig.4, Fig.5 and Fig.6. In order to solve the problem that the culture medium 13 becomes more viscous with increase of fermentation time, the gas spurted from the nozzles 22 generates more violent disturbance to form larger turbulences so as to drive the higher-viscosity culture medium 13 to flow. In the first embodiment, the adjusting tube 24 may be used to adjust the direction of each nozzle 22 in the first space. Via the adjusting tubes 24, the nozzles 22 cooperate to form the flow 17 of the culture medium 13 to make the culture medium 13 circulate and fully mixed inside the vessel 10. In one embodiment, the adjusting tube 24 may be an arc-shape hollow tube rotatably connected with the corresponding channel 38 in a sleeve coupling method. The nozzle 22 is fixed to the adjusting tube 24 and rotates with the rotation of the adjusting tube 24. As shown in Fig.4 and Fig.5, there are four nozzles 22 in the vessel. It is seen from a horizontal view: the nozzles, which are separated by 180 degrees, are simultaneously faced downward (toward the bottom of the vessel) or upward (toward the upper lid). However, The present invention is not limited to ones shown in Fig.4 and Fig.5. The cooperation of the plurality of nozzles 22 may generate more intense flowl7. Hence, although the culture medium 13 becomes more viscous with increase of fermentation time, the sparger 30, which has angle-adjustable nozzles 22, can generate sufficient driving force to make the culture medium 13 circulate well.

[0026] The present invention does not constrain that the form of the sparger must follow the abovementioned embodiments. The quantity and configuration of the nozzles may be varied with the vessel or the requirement. The quantities and configurations of the first connecting pipes and the second connecting pipes may also be varied. The second connecting pipe having the nozzles does not necessarily have the smallest ring radius. In other words, the second connecting pipe is disposed between two first connecting pipes. The pattern of the flow may be established via adjusting the directions of the nozzles.

[0027] Fig.7 is a perspective sectional view schematically showing an air-lift bioreactor according to a second embodiment of the present invention. Refer to Fig.2, Fig.5 and Fig.7. The sparger of the air-lift bioreactor 3 includes a first gas pipe 32, a plurality of first connecting pipes 36, a plurality of channels 38, and a plurality of nozzles 22. The first gas pipe 32 is essentially orthogonal to the first connecting pipes 36 and the channels 38. The first gas pipe 32 is essentially disposed along the central axis of the vessel 10 and parallel to the long axis of the vessel 10. The first gas pipe 32 is extended to the exterior of the vessel 10. The first terminal 31 of the first gas pipe 32 is connected with an exterior device 37. The exterior device 37 may elevate / lower the first gas pipe 32 or rotate the first gas pipe 32. Thus, the exterior device 37 may operate to adjust the altitudes of the first connecting pipes 36, the channels 38 and the nozzles 22 inside the vessel 10. Alternatively, the exterior device 37 may operate to make the channels 38 and the first connecting pipes 36 rotate to-and-fro with the first gas pipe 32 being the axis. Besides, the first connecting pipes 36, the channels 38 and the nozzles 22 may cooperate to form a sparger ring. The first connecting pipes 36 and the channels 38 are essentially on the same horizontal level. A plurality of via-holes is formed on the first connecting pipes 36 (not shown in Fig.7). Some channels 38 are connected with the second terminals 35 of the first gas pipe 32 and have the nozzles 22. The other details of the second embodiment are the same as those of the first embodiment shown in Fig.2 and will not repeat herein. According to requirement, the first terminal 31 of the first gas pipe 32 may be extended out from the upper lid 12 or extended out from the vessel 10. It is easily understood: in the case that the first terminal 31 of the first gas pipe 32 is extended out from the vessel 10, the exterior device can elevate / lower the first gas pipe 32 or rotate the first gas pipe 32 to-and-fro.

[0028] Fig.8 is a perspective sectional view schematically showing an air-lift bioreactor according to a third embodiment of the present invention. Refer to Fig.2, Fig.5, Fig.7, and Fig.8. The sparger of the air-lift bioreactor 5 includes a first gas pipe 32 and two sparger rings 40. The two sparger rings 40 are respectively at different altitudes of the first gas pipe 32. Similarly to the second embodiment shown in Fig.7, the first gas pipe 32 of the air-lift bioreactor 5 may be used to simultaneously or respectively adjust the altitudes of the two sparger rings 40 and / or simultaneously or respectively rotate the two sparger rings 40 inside the vessel 10. The two sparger rings 40 of the air-lift bioreactor 5 may be identical or different in structure. The two sparger rings 40 may respectively have different quantities of the first connecting pipes 36 having the via-holes, the channels 38 and the nozzles 22. Alternatively, the relative positions of the first connecting pipes 36, the channels 38 and the nozzles 22 may be different in the two sparger rings 40. It is easily understood: the air-lift bioreactor 5 may also have a plurality of gas pipes, similar to the first embodiment shown in Fig.2. Besides, the sparger rings 40 of the air-lift bioreactor 5 may have several different patterns of the connecting pipes, which are similar to the first embodiment shown in Fig.2 and will not repeat herein.

[0029] In conclusion, the present invention proposes an air-lift bioreactor, which uses the sparger having the direction-adjustable nozzles to establish an excellent, stable and blind angle-free circulation system, whereby the culture medium having a higher viscosity may be circulated stably and homogeneously inside the vessel. The air-lift bioreactor of the present invention is an agitating blade-free device suitable for shear / cutting-sensitive fermentation.

[0030] The embodiments described above are to demonstrate the technical thought and characteristics of the present invention to enable the person skilled in the art to understand, make and use the present invention. However, these embodiments are not intended to limit the scope of the present invention. Any equivalent modification or variation according to the spirit of the present invention is to be also included by the scope of the present invention.

Claims

CLAIMSWhat is claimed is:

1. An air-lift bioreactor, comprising a vessel, having a first space providing a culture medium to flow thereinside; and a sparger disposed inside the first space of the vessel, wherein the sparger include: a first connecting pipe having a plurality of via-holes disposed thereon; a second connecting pipe, wherein the second connecting pipe and the first connecting pipe are annular and concentrically disposed inside the vessel; a plurality of channels, disposed between and connected with the first connecting pipe and the second connecting pipe; a gas pipe, having a first terminal extended to the vessel and a second terminal extended to at least one of the first connecting pipe, the second connecting pipe, and a portion of the channels; and a plurality of nozzles disposed on at least one of the second connecting and the channels, wherein each nozzle has an adjusting tube, and the adjusting tube is used to adjust an angle of the nozzle in the first space.

2. The air-lift bioreactor according to claim 1, wherein the adjusting tube includes an arcshape hollow tube.

3. The air-lift bioreactor according to claim 1, further comprising an upper lid covering the vessel, wherein the first terminal of the gas pipe is fixed to the upper lid.

4. The air-lift bioreactor according to claim 1, wherein a ring radius of the second connecting pipe is smaller than a ring radius of the first connecting pipe.

5. The air-lift bioreactor according to claim 1, wherein the first terminal of the gas pipe is connected with an exterior device suppling gas to the gas pipe.

6. An air-lift bioreactor, comprising a vessel, having a first space providing a culture medium to flow thereinside; a gas pipe having a first terminal extended to the vessel; and a sparger ring, orthogonal to and disposed on the gas pipe and inside the first space, wherein the sparger ring includes: a first connecting pipe having a plurality of via-holes thereon; and a plurality of channels, disposed between and connected with the first connecting pipe and the gas pipe, wherein the channels have a plurality of nozzles, each nozzle has an adjusting tube, and the adjusting tube is used to adjust an angle of the nozzle in the first space.

7. The air-lift bioreactor according to claim 6, wherein the adjusting tube includes an arcshape hollow tube.

8. The air-lift bioreactor according to claim 6, wherein the sparger ring further comprises a second connecting pipe, wherein the second connecting pipe and the first connecting pipe are annular and concentrically disposed inside the vessel.

9. The air-lift bioreactor according to claim 6, further comprising a plurality of sparger rings, which are disposed on the gas pipe and parallel to each other, wherein one of the sparger rings is fixed to a first terminal of the gas pipe.

10. The air-lift bioreactor according to claim 6, wherein the gas pipe may be elevated / lowered and / or rotated in the first space.

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