Gas lift bioreactor

Abstract

A gas lift bioreactor includes an outer cylinder in which a medium is provided to flow, a fluid multiplier through which a portion of the medium can be accelerated and back into the outer cylinder, and a bubble distributor disposed within the outer cylinder. And the flowing direction of the accelerated culture medium is different from the flowing direction of bubbles generated by the bubble distributor, so that the culture medium has a good recycling effect in the outer cylinder.

Description

TECHNICAL FIELD

[0001] The present invention relates to the field of bioreactors, and in particular to an airlift bioreactor. BACKGROUND

[0002] Broadly, bioreactors can be used to culture microorganisms, plant cells and animal cells. Aeration-agitation bioreactors are used for microbial fermentation and plant cell culture. Airlift bioreactors, when used for microbial culture, can be referred to as airlift fermentors. The general aeration ratio for an airlift bioreactor is about 1 vvm (air volume / culture volume / min). The aeration ratio for animal cell culture is much lower, about 0.05 vvm, due to the lower oxygen demand of animal cells. Such a low aeration ratio results in a slow gas and liquid flow, which cannot form a stable circulation system, and leads to a poor mass transfer rate of oxygen and nutrients, resulting in poor culture efficiency. Therefore, animal cells are still mostly cultured in agitation bioreactors.

[0003] An airlift bioreactor can be divided into four sections, including a riser, a downcomer, a base, and a gas separator. Airlift bioreactors can be used for the culture of suspended cells up to a scale of about 20,000 liters, and for the culture of microorganisms up to a scale of about 1,500,000 liters. However, for media with high viscosity, airlift bioreactors are less suitable due to factors such as rapid energy dissipation and low circulation rate. In addition, in the process of animal cell culture, the gas flow rate is too low to drive the recirculation of media with high viscosity. When the liquid velocity in the downcomer is greater, it is easier to induce more gas bubbles, increasing the gas holdup in the downcomer and the riser.

[0004] Chinese Patent No. CN 202297606U discloses a bioreactor suitable for the self-suspension culture or microcarrier suspension culture of animal cells, which integrates stirring, aeration, and cell filtration to eliminate the shear damage to the cultured animal cells caused by the stirring blades and deep aeration in an agitation bioreactor. Taiwanese Patent No. M531483 discloses a bioreactor system that can improve the circulation efficiency of the culture medium in the device. The system includes an arc-shaped inner bottom surface, a manifold disposed outside the column, and an aeration device connected to the column, achieving airlift circulation and improving the growth efficiency of the culture. SUMMARY

[0005] To solve the above problems, the present application provides a gas lift type bioreactor, which is suitable for a low aeration ratio recirculation system, uses a bubble distributor and a fluid multiplier to create driving power for bubbles and medium recirculation, and has a better circulation effect of the gas lift type bioreactor.

[0006] To solve the above problems, the present application provides a gas lift type bioreactor, which is suitable for a low aeration ratio recirculation system, uses a bubble distributor and a fluid multiplier to create driving power for bubbles and medium recirculation, and has a better circulation effect of the gas lift type bioreactor.

[0007] According to the above, the present application provides a gas lift type bioreactor, which includes: an outer cylinder having a first space to provide a medium flowing therebetween; a fluid multiplier disposed in the first space of the outer cylinder, wherein the fluid multiplier includes a ring body and a fluid inlet and a gap disposed at the ring body, part of the medium enters the ring body from the fluid inlet and flows into the first space from the gap; and a bubble distributor disposed in the first space of the outer cylinder, which generates a plurality of bubbles in the medium, wherein the flow direction of the plurality of bubbles and the flow direction of part of the medium flowing into the first space from the gap are different.

[0008] In an embodiment, a first port of the outer cylinder is opposite to a second port, the fluid multiplier is disposed adjacent to the first port, and the bubble distributor is disposed adjacent to the second port.

[0009] In an embodiment, further including an inner cylinder disposed in the first space of the outer cylinder, wherein the medium flows through a second space provided by the inner cylinder, the ring body of the fluid multiplier is disposed between the inner cylinder and the outer cylinder, and the bubble distributor is disposed in the second space of the inner cylinder.

[0010] In an embodiment, further including an inner cylinder disposed in the first space of the outer cylinder, wherein the medium flows through a second space provided by the inner cylinder, the ring body of the fluid multiplier is disposed in the inner cylinder, and the bubble distributor is disposed between the inner cylinder and the outer cylinder.

[0011] In an embodiment, the ring body of the fluid multiplier is closer to a side wall of the outer cylinder than the bubble distributor.

[0012] In an embodiment, the bubble distributor is closer to a side wall of the outer cylinder than the ring body of the fluid multiplier.

[0013] In an embodiment, the bubble distributor includes a plurality of annular pipe bodies, a plurality of communication channels and a gas inlet port, the plurality of communication channels communicate the plurality of annular pipe bodies, and the plurality of annular pipe bodies are provided with a plurality of bubble openings.

[0014] In one embodiment, the plurality of annular tubes are arranged in a concentric manner.

[0015] In one embodiment, the bubble sparger is made of metal or plastic material.

[0016] In one embodiment, the fluid multiplier is used to accelerate the portion of the culture medium flowing therethrough. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 Assembled perspective view of a first embodiment of the gas lift bioreactor of the present invention.

[0018] Figure 2 Exploded view of a first embodiment of the gas lift bioreactor of the present invention. Please refer to

[0019] Figure 3 Top view projection of a first embodiment of the bubble sparger of the present invention.

[0020] Figure 4 Perspective side view of a first embodiment of the bubble sparger of the present invention.

[0021] Figure 5 Top view projection of a first embodiment of the fluid multiplier of the present invention.

[0022] Figure 6 Perspective side view of a first embodiment of the fluid multiplier of the present invention.

[0023] Figure 7 Partial cross-sectional side view of a first embodiment of the fluid multiplier of the present invention.

[0024] Figure 8 Assembled perspective view of a second embodiment of the gas lift bioreactor of the present invention.

[0025] Figure 9 Assembled perspective view of a third embodiment of the gas lift bioreactor of the present invention.

[0026] Figure 10 Assembled perspective view of a fourth embodiment of the gas lift bioreactor of the present invention. DETAILED DESCRIPTION

[0027] Figure 1 Assembled perspective view of a first embodiment of the gas lift bioreactor of the present invention, Figure 2 Exploded view of a first embodiment of the gas lift bioreactor of the present invention. Please refer to Figure 1 and Figure 2The main components of the gas-lift bioreactor 1 include an outer cylinder 10, an inner cylinder 20, a sparger 30, and a flow amplifier 40. The outer cylinder 10 provides a first space 11 in which the inner cylinder 20, the sparger 30, and the flow amplifier 40 are disposed, and a medium required for cell culture flows therebetween, with a liquid level 19 higher than the flow amplifier 40. In the first embodiment, the inner cylinder 20 also provides a second space 21 for providing a passage for the medium. The outer cylinder 10 and the inner cylinder 20 are in a similar sleeve connection, with a portion of the first space 11 left between the side wall 16 of the outer cylinder 10 and the side wall 26 of the inner cylinder 20, and the first space 11 and the second space 21 being in communication. Further, the open first port 22 of the inner cylinder 20 is adjacent to the first port 12 of the outer cylinder 10, and the open second port 24 of the inner cylinder 20 is adjacent to the second port 14 of the outer cylinder 10. The flow amplifier 40 is disposed on the inner cylinder 20 and adjacent to the first port 22 of the inner cylinder 20, and the sparger 30 is disposed between the outer cylinder 10 and the inner cylinder 20 and adjacent to the second port 24 of the inner cylinder 20, with the first port and the second port being opposite to each other. Furthermore, the outer cylinder 10 can be provided with a communication passage (not shown in the figure) for connecting a flow pipe and equipment (not shown in the figure) outside the cylinder. The first port 12 of the outer cylinder 10 can be provided with a cover (not shown in the figure) or a design for connecting the flow pipe and equipment outside the cylinder, so that the medium can be circulated back into the gas-lift bioreactor 1 by using the flow pipe and equipment outside the outer cylinder 10. For the convenience of description, in the following paragraphs, the first port is referred to as the top of the gas-lift bioreactor 1, and the second port is referred to as the bottom of the gas-lift bioreactor 1. For the purpose of clearly illustrating the features of the present application, the communication passage of the outer cylinder 10 outside the cylinder is simplified or not shown in the figure, which is not intended to limit the gas-lift bioreactor 1 of the present application.

[0028] Figure 3 A top view schematic diagram of the first embodiment of the sparger of the present application, Figure 4 A perspective side view schematic diagram of the first embodiment of the sparger of the present application. Reference is made to Figure 1 、 Figure 2 、 Figure 3 and Figure 4The bubble sparger 30 increases oxygen transfer and contributes to recirculation driving force in the gas lift bioreactor 1 by increasing gas flow area and reducing bubble size. The bubble sparger 30 can include a plurality of hollow tubes 32 arranged concentrically, and one or more communication passages 34 can be arranged between the tubes 32 to connect the tubes 32 and stabilize the entire bubble sparger 30. A gas inlet 36 is provided on one of the tubes 32 to connect an external gas injection device (not shown) to inject gas from the gas injection device into the connected tubes 32, and the injected gas enters each of the tubes 32 through the communication passages 34. In one embodiment, a plurality of bubble openings 38 are provided on the tube wall of each of the tubes 32, and the gas passing through the tubes 32 escapes from the bubble openings 38 into the culture medium between the outer cylinder 10 and the inner cylinder 20 to generate upward flow. The tubes 32 can be made of metal, plastic or other suitable materials, and the number of concentric rings formed by the tubes 32 is not limited to that shown in the figure. The more the number of rings, the more the area for providing the bubble openings 38. The distribution of the bubble openings 38 on the tubes 32 can be regular or irregular. For example, the regular distribution can be arranged along the circumference of the tubes 32 at a fixed interval, and the irregular distribution can adjust the density of the bubble openings 38 at different positions of the tubes 32 or on different tubes 32. In addition, the sizes of the bubble openings 38 can be the same or different, and smaller openings can form smaller bubble sizes.

[0029] Figure 5 is a top view schematic diagram of a first embodiment of a fluid multiplier of the present invention, Figure 6 is a perspective side view schematic diagram of a first embodiment of a fluid multiplier of the present invention. Figure 7 is a partial cross-sectional side view schematic diagram of a first embodiment of a fluid multiplier of the present invention. Reference is made to Figure 1 、 Figure 2 、 Figure 5 、 Figure 6 and Figure 7The fluidic multiplier 40 includes a hollow ring 42 and a fluid inlet 46 communicating with a space 45 enclosed by the ring 42. The height h of the space 45 can be adjusted according to design, and the inner side wall 44 of the ring 42 is provided with a gap 47 (not shown in the figure) communicating with the space 45 enclosed by the ring 42. The inner side wall 44 is slightly inclined and protruding, so that the fluid flowing through the inner side wall 44 of the fluidic multiplier has a longer route than the outer side wall, thereby forming a negative pressure zone to attract the fluid above to flow downward. In other words, the space 45 is thicker near the gap 47 and thinner away from the gap 47. In addition, the fluid inlet 46 provides the medium flowing back from the outer flow pipe (not shown in the figure) into the fluidic multiplier 40. The arrangement of the space 45 enclosed by the ring 42 and the gap 47 can increase the pressure of the medium flowing therethrough to generate a thrust, thereby creating a negative pressure zone to drive the intermediate flow 15 outside the inner cylinder 20 near the first port 12 to flow into the space 21 of the inner cylinder 20 at a high speed. The thrust of the fluidic multiplier 40 also drives the medium in the space 21 of the inner cylinder 20 to flow downward at a high speed and reach the bottom of the inner cylinder 20 and the outer cylinder 10 (the second port 14), thereby facilitating the recirculation of the medium. The arrangement of the fluidic multiplier of the present application can further highlight the acceleration effect on the medium with a larger viscosity.

[0030] Figure 8 Figure 6 is a perspective view of the assembled gas lift bioreactor according to a second embodiment of the present application. Please refer to Figure 1 、 Figure 2 and Figure 8 , and Figure 1 Compared with the first embodiment, the gas bubble distributor 30 of the gas lift bioreactor 3 is arranged in the inner cylinder 20 and adjacent to the open second port 24 of the inner cylinder 20. The fluidic multiplier 40 is arranged between the outer cylinder 10 and the inner cylinder 20 and adjacent to the open first port 22 of the inner cylinder 20 and the first port 12 of the outer cylinder 10. The structures of the other components are similar to those of the first embodiment, and thus are not described here. Therefore, the upward flow 13 of the gas lift bioreactor 3 is in the inner cylinder 20, the intermediate flow 15 is from the inner cylinder 20 to the outside of the inner cylinder 20, and the downward flow 17 is between the outer cylinder 10 and the inner cylinder 20.

[0031] According to the above, the gas lift bioreactor of the present application builds an excellent, stable, and dead-angle-free circulation system by arranging the gas bubble distributor and the fluidic multiplier. The medium has a stable and uniform flow rate at each position of the outer cylinder and the inner cylinder for circulation. The gas bubble distributor increases the oxygen transmission in the gas lift bioreactor and contributes to the recirculation driving force by increasing the gas flow area and reducing the bubble size. The fluidic multiplier creates a negative pressure zone to generate a driving force to accelerate the fluid flow rate by using the difference in fluid flow.

[0032] Figure 9Fig. 4 is a perspective view of the assembled gas lift bioreactor of the third embodiment of the present application. Please refer to Figure 1 、 Figure 2 、 Figure 5 、 Figure 7 、 Figure 8 and Figure 9 , and the first embodiment and the second embodiment, the gas lift bioreactor 2 has no inner cylinder, and the height h of the ring body of the fluid multiplier 50 is increased, wherein the relative sizes of the bubble distributor 30 and the fluid multiplier 50 can be designed to arrange the distribution areas of the upward flow 13 and the downward flow 17 in the outer cylinder 10. For example, if the projected area of the bubble distributor 30 is larger than that of the fluid multiplier 50 as viewed from the top, the upward flow 13 can be caused to approach the side wall of the outer cylinder 10 more than the downward flow 17, or in other words, the upward flow 13 of the culture medium in the first space 11 of the outer cylinder 10 surrounds the downward flow 17, the intermediate flow 15 approaching the top (the first port 12) flows from the side wall to the center of the cylinder, and the intermediate flow 15 approaching the bottom (the second port 14) flows from the center to the side wall of the cylinder, so that the culture medium forms a dead angle-free circulation in the entire first space 11 of the outer cylinder 10. On the other hand, by increasing the height h of the ring body of the fluid multiplier 50, not only the space 45 of the fluid multiplier 50 is increased to accelerate the downward flow 17, but also a boundary is formed between the downward flow 17 and the upward flow 13 to prevent the mixing of the two flows. Therefore, the fluid multiplier 50 can replace the inner cylinder of a general gas lift bioreactor, simplify the structure of the gas lift bioreactor, increase the use and amplification flexibility of the gas lift bioreactor, and facilitate the culture of animal cells, but not limited to the culture of animal cells, and can also be suitable for the culture of other suspended cells.

[0033] Figure 10 Fig. 5 is a perspective view of the assembled gas lift bioreactor of the fourth embodiment of the present application. Please refer to Figure 1 、 Figure 2 、 Figure 5 、 Figure 7 、 Figure 8 、 Figure 9 and Figure 10Compared to the third embodiment, the air-lift bioreactor 4 also lacks an inner cylinder. Viewed from above, the projected area of ​​the bubble distributor 30 is smaller than that of the fluid multiplier 50. The upward flow 13 is closer to the center of the outer cylinder 10 than the downward flow 17. Alternatively, it can be said that within the first space 11 of the outer cylinder 10, the downward flow 17 of the culture medium surrounds the upward flow 13. The intermediate flow 15 near the top flows from the center of the cylinder to the side wall, while the intermediate flow 15 near the bottom flows from the side wall to the center. This creates a complete circulation of the culture medium within the first space 11 of the entire outer cylinder 10. Understandably, the fluid multiplier of the air-lift bioreactor 4 can be a fluid multiplier with different annular heights h compared to the first and second embodiments. Furthermore, in the air-lift bioreactor embodiment omitting the inner cylinder, the position of the fluid multiplier within the outer cylinder can be adjusted according to the height of the culture medium, as long as the culture medium height covers the fluid multiplier. Furthermore, it is understood that the fluid multiplier of the air-lift bioreactor of the present invention can also be used with conventional bubble distribution components / equipment, and is not limited to the aforementioned bubble distributor. Therefore, in the air-lift bioreactor embodiment that omits the inner cylinder, the amount of culture medium is not limited by the actual height of a typical inner cylinder, providing greater flexibility in the design of the culture environment.

[0034] The embodiments described above are merely for illustrating the technical ideas and features of the present invention, so that those skilled in the art can understand, manufacture and use the present invention. However, these embodiments are not intended to limit the patent scope of the present invention. Any equivalent modifications or changes made in accordance with the spirit and principles of the present invention should still be covered within the patent scope of the present invention.

Claims

1. An air-lift bioreactor, wherein, include: An outer cylinder having a first space for providing a culture medium to flow therein; A fluid multiplier is disposed in the first space of the outer cylinder, wherein the fluid multiplier includes a ring body and a fluid inlet and a slit disposed at the ring body, and a portion of the culture medium enters the ring body from the fluid inlet and flows into the first space from the slit; as well as A bubble distributor is disposed in the first space of the outer cylinder, which generates multiple bubbles in the culture medium, wherein the flow direction of the multiple bubbles is different from the flow direction of the portion of the culture medium flowing into the first space from the gap.

2. The airlift bioreactor of claim 1, wherein a first port of the outer cylinder is opposite a second port, the fluid multiplier is disposed adjacent to the first port, and the bubble distributor is disposed adjacent to the second port.

3. The air-lift bioreactor as described in claim 2, wherein, It also includes an inner cylinder disposed within the first space of the outer cylinder, wherein the culture medium flows through a second space provided by the inner cylinder, the annulus of the fluid multiplier is disposed between the inner cylinder and the outer cylinder, and the bubble distributor is disposed within the second space of the inner cylinder.

4. The air-lift bioreactor as described in claim 2, wherein, It also includes an inner cylinder disposed within the first space of the outer cylinder, wherein the culture medium flows through a second space provided by the inner cylinder, the annulus of the fluid multiplier is disposed within the inner cylinder, and the bubble distributor is disposed between the inner cylinder and the outer cylinder.

5. The air-lift bioreactor of claim 2, wherein the annulus of the fluid multiplier is adjacent to one side wall of the outer cylinder compared to the bubble distributor.

6. The air-lift bioreactor of claim 2, wherein the bubble distributor is located closer to one side wall of the outer cylinder than to the annulus of the fluid multiplier.

7. The air-lift bioreactor as described in claim 1, 2, 3, 4, 5 or 6, wherein the bubble distributor comprises a plurality of annular tubes, a plurality of connecting channels and a gas inlet communicating with each other, the plurality of connecting channels connecting the plurality of annular tubes, and the plurality of annular tubes having a plurality of bubble openings.

8. The air-lift bioreactor of claim 7, wherein a plurality of the annular tubes are arranged in a concentric circle.

9. The air-lift bioreactor of claim 7, wherein the bubble distributor is made of metal or plastic material.

10. The airlift bioreactor as claimed in claim 1, 2, 3, 4, 5 or 6, wherein the fluid multiplier is used to accelerate the flow of a portion of the culture medium therethrough.

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