GB2032956A

GB2032956A - Bioreactor and Method of Performing Bioreactions

Info

Publication number: GB2032956A
Application number: GB7932912A
Authority: GB
Original assignee: Luwa Ltd
Current assignee: Luwa Ltd
Priority date: 1978-09-22
Filing date: 1979-09-21
Publication date: 1980-05-14
Also published as: DE2936092A1; JPS5589750A; CH642679A5; GB2032956B

Abstract

A bioreactor possesses a reaction chamber formed by a substantially ring-shaped tube or pipe having a substantially circular cross-sectional configuration. A hollow shaft (12), carrying a drive screw (14), is arranged within the reaction chamber tangentially with respect to the centre line (11) of the pipe (2). This hollow shaft is operatively connected with a drive motor and, furthermore, is provided with outlet connections or studs communicating with a gas source. The pipe 2 is provided over part of its circumference with an equally circular or ring-shaped jacket or shell through which flows a heat exchange medium, namely a heating or cooling medium. <IMAGE>

Description

SPECIFICATION Bioreactor and Method of Performing Bioreactions The present invention relates to a bioreactor, a method of performing bioreactions and a method of separating foam from a bioreaction mass.

Bioreactors are known which comprise a reaction chamber or compartment delimited by a vessel and defining a recirculation path, with drive means serving to maintain in circulation the reaction mass contained within the reaction chamber.

Heretofore known bioreactors of this type, which are in the experimental stage, comprise an upright, for instance essentially cylindrical vessel, which contains a coaxially arranged guide tube.

The reaction mass is maintained in circulation either by means of a stirrer or by means of a liquid pump producing a propellent jet and propelled through a gasification zone. The guide tube constitutes a defined circulation path which produces a favourable constriction of the residence time spectrum and the supply of the cells. Hence, with bioreactors of this type it is possible to achieve noteworthy results as concerns production quality and specific production output.

The prior tests have already demonstrated that maintaining the circulation flow, especially the attainment of sufficiently high oxygen-transfer coefficients, requires an appreciable specific drive output. Apart from the foregoing there is required an appreciable amount of energy if it is not intended to work with many undesirable inhibitors, and equally, also for foam separation or destruction. Moreover, it is to be observed that the proportion of cells which are entrained in the wet foam is comparatively great and that these cells are inadequately nourished so that there exists the danger of cell atrophy.

According to a first aspect of the present invention there is provided a bioreactor comprising: a vessel having therein a reaction chamber defining a recirculation path of travel for a reaction mass: drive means for maintaining the reaction mass in circulation within the reaction chamber; wherein the vessel comprises a substantially horizontally extending closed pipe loop, the pipe loop comprising a pipe having throughout its circumference an at least approximately constant cross-sectional area and shape; and the drive means is arranged to impart a predominantly turbulent flow characteristic to the reaction mass during its circulation through said pipe loop.

According to a second aspect of the present invention there is provided a method of forming bioreactions in a closed vessel. comprising the steps of. placing in a closed vessel a reaction mass suspension comprising a nutrient substrate solution in which there are suspended cells: feeding an oxygen-containing gas into the vessel for contact with the reaction mass suspension: circulating the reaction mass suspension within the vessel while infeeding the oxygen-containing gas; and guiding the reaction mass suspension to flow in a substantially ring-shaped path with predominantly turbulent flow characteristic.

According to a third aspect of the present invention there is provided a method of separating foam from bioreaction mass during a bioreaction, comprising the steps of: imparting a circulatory flow to the bioreaction mass along a substantially ring-shaped path of travel; superimposing a rotational movement upon the bioreaction mass which flows along said ringshaped path of travel and about the centre line of said path of travel, thereby to produce shear forces which act on foam separated out of the reaction mass.

Thus in the present invention the bioreactor of the present development is manifested by the features that the vessel comprises a closed pipe or tube loop which extends essentially horizontally, the pipe having, throughout its circumference, an at least approximately constant cross-sectional surface and shape. The drive means are structured such that there is imparted to the reaction mass, during its circulation or movement through the pipe loop, a predominantly turbulent flow characteristic or behaviour.

Consequently, the reaction chamber of the inventive bioreactor defines a circulation path to which there are applied impulses and in which there are avoided dead water zones.

A particularly homogeneous flow characteristic can be achieved if the pipe or tube loop has the form of a circular ring. In any event, however, owing to the forced circulation of flow and the turbulence of the flow there are obtained almost ideal nourishment and admixing conditions.

Consequently, there can be attained gas-transfer coefficients kLa up to 800 h-l with a specific energy consumption for the drive and gas input of less than 4W l-1.

A construction of reactor which has been found to be particularly advantageous includes a tube or pipe having a circular cross-section and means for imparting a screw-line or helical-shaped course to the product flow or stream which flows in the circular-shaped path.

During operation of a bioreactor embodying the invention it has surprisingly been found that the formation of foam is exceptionally small. In particular, it has been discovered that for the interesting flow velocities of, for instance, 0.5 m sec.-' the formation of foam is less than with smaller flow velocities, which do not produce adequate intensive circulation or admixing and cell supply or nourishment. This surprising phenomenon can be explained in terms of the fact that the reaction mass, which is propelled at a relatively high flow velocity through the ringshaped pipe or tube ivop produces appreciable shear forces on the foam The foam collecting at the inner wall or inner surface of the ring or circular pipe by virtue of the centrifugal separation effect, experiences a shearing action between the reaction mass and the pipe wall.

Therefore, the rotational movement of the product flow about the axis of the path of travel does not cause propulsion of the foam along a path of constant free cross-sectional area, but rather in a gap which tapers approximately in a wedgeshaped configuration, terminating at that location where the reaction mass again contacts the pipe wall. At this zone not only shearing forces but also compressive forces act on the foam bubbles.

Thus, due to the shearing action and also the compressive action the foam bubbles are fractured or destroyed. At the free cross-sectional area it is therefore possible for only relatively dry foam to reside throughout a longer period of time, the content of cells in such relatively dry foam being negligible. It has been found that at least in individual cases it is possible to dispense with the use of a conventional foam separator or, as the case may be, such need not be placed into operation.

The invention will be further described with reference to the accompanying drawings, in which Figure 1 is a horizontal sectional view of a bioreactor embodying the invention, the sectional view being taken substantially along the line I-I of Figure 2; and Figure 2 is a vertical sectional view, taken substantially along the line li-li of the apparatus of Figure 1.

In the drawings, reference character 2 designates the vessel or container of a bioreactor which contains a reaction chamber or compartment 4. The vessel 2 is formed by an essentially horizontally arranged, closed pipe or tube loop in the form of a circular ring or pipe 2a, this pipe possessing a substantially circular crosssectional configuration. As best seen by referring to Figure 2, the bioreactor has a heat exchange jacket or shell 6, namely a cooling or heating jacket, surrounding the pipe or tube 2a over part of its circumference and extending along the entire pipe loop. Reference character 8 designates a pipe conduit or line and reference character 10 a valve of the schematically indicated circulation system for the cooling or heating medium, as the case may be.

Extending tangentially with respect to the pipe axis 11, i.e. the centre line of the pipe 2, within the reaction chamber 4, is a hollow shaft 12.

Carried at the free end of the hollow shaft 12 is a drive element, here shown as a drive screw or worm 14 or equivalent structure. The hollow shaft 12, extending at location 1 6 through the wall 2b of the vessel 2, is mounted in a conventional manner in a flange body 1 8 which is secured to the outer wall 2c of the vessel 2. An electric drive motor 20, e.g. a direct-current motor, is operatively connected by means of its housing 20a with the flange body 18, and the motor shaft is operatively coupled with the hollow shaft 12.

Connected with the flange body 1 8 is a gas supply line or source 22 which is flow connected in any suitable fashion with the interior of the hollow shaft 12. The hub 1 4a of the drive screw 14 carries a multiplicity of connection pieces or studs 24 or equivalent structure serving for the gas infeed. These connection pieces 24 are connected with the interior of the hollow shaft 12 and open into the reaction chamber or compartment 4.

The arrow 26 indicates the direction of circulation of the flow of the reaction mass with which the reaction chamber 4 is filled and brought about by the action of the drive screw 14 or equivalent structure. In the flow direction forwardly of the drive screw 14 the reaction chamber 4 is connected, by means of an upwardly protruding connnection or stud 28 or the like, with a conventional foam separator 30. The foam separator 30 is equipped with a standard drive motor 32.To simplify the illustration the openings or connections of the vessel, serving for filling and emptying, i.e. for the addition and removal as well as for the inoculation of the reaction mass, and equally the devices seving for measurement and monitoring, have been omitted, particularly since such structure may be conventional and is unimportant for understanding the underlying principles and concepts of the present invention.

The drive screw 14 and its drive are designed such that there is produced a turbulent flow in the bioreaction mass, which generally moves or circulates in the direction of the arrow 26.

Moreover, by virtue of the design and arrangements of the drive, i.e. the drive screw, there is imparted to the product flow a rotational movement about the axis of its path of travel, so that the flow moves along an essentially screw or helicai-shaped path. During each passage of a flow cross-section i.e. a sectional portion of the reaction mass through the drive zone constituted by the drive screw 14, there is accomplished an infeed of sucked-up gas or gas which is fed in at excess pressure. The dispersion of such gas into the reaction mass has already progressed extensively by the time the reaction mass leaves the drive zone by virtue of the rotation of the connection studs 24 and the turbulence of the flow.By virtue of the uniform geometric shape of the vessel it is possible for the turbulent motion imparted to the reaction mass to be maintained as it passes around the vessel and the horizontal arrangement of the vessel augments the homogeneity of the product flow over the circulation path. The rotational movement of the flow about the path axis, i.e. the centre line 11 of the reaction chamber 4 counteracts the tendency of the gas bubbles to ascend out of the liquid phase, and thus their residence time in the liquid phase is prolonged, with the result that the infed gas can fulfill its nourishing or supply functions with good efficiency.

In Figure 2 the arrow 34 schematically indicates the rotational movement of the product flow about the path axis 11. i.e. the centre line of the reaction chamber 4, within the reaction mass 36 The foam which collects at location 38'above the reaction mass, as mentioned, is to a large degree continuously dispersed by the action of shearing and compressive forces. The foam separator 30 therefore need only be brought into operation in the presence of intensively foaming reaction masses.

The illustrated bioreactor is particularly easy to sterilize, due to its uniform geometric shape. In particular, when the drive is not carried out by a drive screw, it is then possible to provide at one or a number of spaced cross-sectional regions of the pipe loop screw or helical-shaped guide elements, generally schematicaliy indicated in Figure 2 by reference character 50, which impart a screw or helical-shaped path of travel to the product flow.

Particularly at those locations where the pipe loop forms a relatively long circulation path, it can be advantageous to use, in addition, to a drive screw, a number of such guide elements 50.

When using helical-shaped guide elements it is also possible to obtain uniform flow conditions in an elongated O-shaped or oval pipe loop by placing the guide elements arranged at the linear or only slightly curved connection sections between the curved or arcuate sections. Instead of or in addition to such guide elements it is also possible to arrange driven screws or worms in each of the connection elements or sections.

Instead of accomplishing gas insertion through the hollow shaft of the drive screw or worm, as in the illustrated embodiment, it is possible to structure the corresponding infeed elements in the form of stationary connection pieces or studs which are arranged downstream of the drive screws or worms and/or the screw or helicalshaped guide elements.

By virtue of its comparatively large vessel surface the illustrated bioreactor is particularly also suitable for the performance of photosynthesis processes, wherein it is possible to provide light sources which are distributed over the entire circumference. In a very simple construction, the light sources can be light transmitting wall portions of the vessel, merely schematically indicated in Figure 2 by reference character 60.

Claims

1. A bioreactor comprising a vessel having therein a reaction chamber defining a recirculation path of travel for a reaction mass; drive means for maintaining the reaction mass in circulation within the reaction chamber; wherein the vessel comprises a substantially horizontally extending closed pipe loop, the pipe loop comprising a pipe having throughout its circumference an at least approximately constant cross-sectional area and shape; and the drive means is arranged to impart a predominantly turbulent flow characteristic to the reaction mass during its circulation through said pipe loop.

2 A bioreactor as defined in claim 1, wherein the pipe possesses a substantially circular crosssectional configuration.

3. A bioreactor as defined in claim 1 or 2, wherein said pipe comprises a substantially circular ring member.

4. A bioreactor as defined in any one of claims 1 to 3 and including means provided for said pipe for imparting to the reaction mass a flow along a substantially screw-shaped path of travel.

5. A bioreactor as defined in claim 4, wherein said means for imparting said substantially screwshaped path of travel to the reaction mass comprises a drive screw of the drive means, the drive screw having a shaft extending approximately tangentially with respect to said pipe axis.

6. A bioreactor as defined in claim 5, wherein said means for imparting said substantially screwshaped path of travel to said reaction mass comprises at least one stationary, substantially screw-shaped guide element.

7. A bioreactor as defined in claim 5 or 6, wherein the shaft of the drive means is hollow, the hollow shaft having a driven end located externally of the vessel, and a gas infeed is arranged to pass gas to the reaction chamber via the hollow shaft.

8. A bioreactor as defined in any one of preceding claims, and including a heat exchange jacket surrounding at least part of the circumference of said pipe.

9. A bioreactor as defined in claim 8, wherein said heat exchange jacket comprises a cooling jacket.

10. A bioreactor as defined in claim 8, wherein said heat exchange jacket means comprises a heating jacket.

11. A bioreactor as defined in any one of the preceding claims and including light source means provided for said reactor chamber.

12. A bioreactor as defined in any one of the preceding claims, wherein the pipe loop comprises curved sections and connection sections; and the connection sections contain means for imparting to the reaction mass a substantially screw-shaped path of travel.

13. A bioreactor as defined in claim 12, wherein said connection sections are substantially straight.

14. A bioreactor as defined in claim 12, wherein the connection sections are slightly curved.

1 5. A bioreactor as defined in claim 12, wherein said curved sections comprise two approximately semicircular sections.

16. A bioreactor as defined in claim 12, wherein said connection sections contain stationary screw-shaped guide elements.

1 7. A bioreactor as defined in any one of the preceding claims and including a plurality of gas inlet connections distributively arranged over the extent of the pipe loop.

18. A method of forming bioreactions in a closed vessel, comprising the steps of: placing in a closed vessel a reaction mass suspension comprising a nutrient substrate solution in which there are suspended cells; feeding an oxygencontaining gas into the vessel for contact with the reaction mass suspension, circulating the reaction mass suspension within the vessel while infeeding the oxygen-containing gas; and guiding the reaction mass suspension to flow in a substantially ring-shaped path with predominantly turbulent flow characteristic.

19. A method as defined in claim 18, and including the step of: generating a substantially screw-shaped movement of the reaction mass suspension in said ringshaped flow.

20. A method of separating foam from a bioreaction mass during a bioreaction, comprising the steps of: imparting a circulatory flow to the bioreaction mass along a substantially ringshaped path of travel; superimposing a rotational movement upon the bioreaction mass which flows along said ring-shaped path of travel and about the centre line of said path of travel, thereby to produce shear forces which act on foam separated out of the reaction mass.

21. A bioreactor constructed and arranged to operate substantially as hereinbefore described with reference to and as illustrated in the accompanying drawings.

22. A method of forming a bioreaction substantially as hereinbefore described with reference to and as illustrated in the accompanying drawings.

23. A method of separating foam from a bioreaction substantially as hereinbefore described with reference to and as illustrated in the accompanying drawings.