WO1996027656A1 - Bioreacteur a surface agrandie - Google Patents

Bioreacteur a surface agrandie Download PDF

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Publication number
WO1996027656A1
WO1996027656A1 PCT/IB1996/000157 IB9600157W WO9627656A1 WO 1996027656 A1 WO1996027656 A1 WO 1996027656A1 IB 9600157 W IB9600157 W IB 9600157W WO 9627656 A1 WO9627656 A1 WO 9627656A1
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WO
WIPO (PCT)
Prior art keywords
bioreactor
culture suspension
bioreactor according
sloping surface
suspension
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB1996/000157
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German (de)
English (en)
Inventor
Anton Kühne
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Individual
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Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of WO1996027656A1 publication Critical patent/WO1996027656A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/02—Stirrer or mobile mixing elements

Definitions

  • the present invention relates to a bio-technological reactor, in particular for the submerged process.
  • Bioreactors must be designed in such a way that the process-optimal conditions in terms of temperature, pH value and nutrient concentration can be established.
  • the tasks of a bioreactor therefore include the mass transfer within the liquid phase (by mixing), the dispersion of a second phase, usually air, in order to obtain a large phase interface for good mass transfer (divide) and the heat transfer to both dissipate the heat of reaction as well as the heat generated when mixed with mechanically moving internals.
  • the design of a bioreactor depends on its area of application and must take into account the specific requirements of the biological system used. This applies particularly to culture suspensions. Today, most procedures are carried out submerged. Because of their versatility, mechanically stirred reactors are used most frequently as sub ers reactors.
  • the minimal equipment of a mechanically stirred reactor currently in use comprises a pressure vessel, an agitator, a gas feed line which enables the gas to be fed into the culture suspension at the bottom, a feed for nutrient medium and a feed for acid or. Alkali and the corresponding derivatives.
  • Monitoring devices are also required for optimal process control, for example probes for pH determination, the determination of the redox potential and the partial pressures, for example of oxygen and carbon dioxide, sensors for temperature and pressure etc.
  • a bioreactor in the form of a horizontal cylinder with a horizontally arranged stirrer shaft (horizontal bioreactor) is used, which has large stirring blades and its filling volume in this way is that part of the stirring blade periodically passes from the liquid phase into the gas phase, a thin film of the culture suspension adhering to the stirring blade, on which the oxygen absorption takes place at least partially.
  • the oxygen supply is preferably carried out exclusively above the surface of the liquid.
  • the object of the present invention is therefore to provide a bioreactor with good mixing properties, in which the oxygen supply is ensured with low foaming and low shear forces, particularly in the submerged process. Further objects of the present invention are the provision of a method for operating such a bioreactor and the use of the special bioreactor. These objects are achieved by a bioreactor with the features described in claim 1, i.e. a bioreactor, which is characterized in that it has at least one surface which at least temporarily extends essentially within the head space and falls in the direction of the culture suspension surface, and has a means for conveying culture suspension from the floor space into the head space. Preferred embodiments are defined in the subclaims.
  • the bioreactor according to the invention has the advantage that the oxygen uptake can be increased compared to known reactors, in particular in the case of the vertical bioreactor, with a simultaneous reduction in the foam formation and the stirring speed, as a result of which the shear forces and thus the destruction of the cells decrease sharply.
  • FIG. 1 shows a cross section through a
  • Horizontal bioreactor with a horizontally arranged stirrer shaft and with an immovably attached surface in the form of a cylinder segment that extends essentially within the head space and falls in the direction of the culture suspension surface.
  • Figure 2 shows a cross section through the same bioreactor but with a movably attached sloping surface.
  • Figure 3 shows a longitudinal section through the reactor of Figure 2.
  • FIG. 4 shows a vertical bioreactor with a surface in the form of a cone, which extends essentially within the head space and falls in the direction of the culture suspension surface.
  • Figure 5 shows a vertical bioreactor in which the wall of the reactor itself is included in the sloping surface.
  • the bioreactors according to the invention have all the constituents customary in conventional bioreactors, such as liquid and gas feed and discharge lines, stirring and heating means, measuring probes, etc. It is essential that the reactors according to the invention have at least one component at least temporarily have surface 1 (falling surface) which essentially extends within the head space and slopes in the direction of the liquid surface, and a means for transporting cultural suspension 2 (means of transport) from the floor space 3 onto the falling surface 1. Below the floor space 3 the region of the reactor space is understood here in which the culture suspension (culture broth) collects in the idle state.
  • the area of the reactor designated by the term head space 4 comprises the gas space.
  • the means for conveying culture suspension 2 (means of transport) from the floor space 3 of the reactor via the sloping surface 1 can be, for example in the case of the horizontal bioreactor, the agitator shaft 6, which rotates the sloping surface 1, for example a cylinder segment, or can comprise at least one pump 21, with at least one feed line 22 immersed in the culture broth and optionally at least one discharge line 23, and at least one outlet passage opening 24, which is arranged above the at least one sloping surface 1 in the head space 4.
  • the means for transporting culture suspension 2 is preferably a means for periodically immersing and / or immersing the sloping surface 1 in the culture suspension.
  • At least one gas supply 5 is preferably arranged above the surface of the culture suspension, so that foam formation due to (intensive) gassing from below is avoided.
  • the at least one sloping surface 1 can take very different forms. For example, it can be an inclined plane, or it can be conical or dome-shaped.
  • the inner surface of the wall of the reactor can also be at least part of a sloping surface, for example an inclined plane (cf. FIG. 5).
  • Immovable fixation is beispiels ⁇ , for a horizontal-bioreactor, wherein the optimal surface enlargement means corresponding to the shape of the outer wall formed hollow cylinder sections er ⁇ aims "is.
  • the supply of the culture suspension is preferably via meh ⁇ eral output openings 24 along the reactor length.
  • a movable sloping surface 1 can also be provided in the horizontal bioreactor, in which the material is applied by immersing the sloping surface 1 attached to the stirrer shaft 6 and thereby rotated parallel to this.
  • the at least one sloping surface 1 can also be immovably attached or else movable, e.g. by fastening to a stirrer shaft 6.
  • the oxygen uptake of the suspension can be improved since, on the one hand, the culture suspension is better distributed and, in addition, a countercurrent effect is generated.
  • the stirring in the bio-reactors according to the invention is only intended to prevent the cells from sinking, it may be sufficient if stirring is carried out in the lower region of the floor space, so that the sloping surface 1 can also be immersed in the vertical bioreactor to accommodate culture suspension.
  • Such immersion can take place, for example, in the case of a short stirrer shaft 6 by means of a conveyor shaft arranged transversely to the stirrer shaft 6 and above it, on which the sloping surface, for example a ball, is arranged.
  • sloping surfaces e.g. a plurality of conical surfaces or inclined planes are arranged one above the other and / or next to one another, the amount of culture suspension which is applied to the sloping surface being such that part of the culture suspension is in each case on the upper sloping surface Surface distributed, while another part reaches the underlying surface and is also distributed there, so that a thin, preferably a cell thick layer is formed.
  • This division of the culture suspension can, for example in the case of conical or dome-shaped sloping surfaces, by means of an annular overflow in the region of the cone or. Dome tip take place, or through openings in the respective sloping surface above, e.g. Holes, slots, etc.
  • the nature of the sloping surface can also be different.
  • the surface thereof is preferably smooth. However, it can also consist of a fine-pored material through which gas diffuses and enables additional contact of the suspension film with oxygen.
  • the sloping surface can be provided with openings which allow the liquid to be dispensed to those arranged below allow sloping surfaces, or have grooves that affect the dwell time.
  • the bioreactor according to the invention is particularly suitable for the cultivation of animal cells, but also for all microorganisms and other uses in the reactor.
  • At least one cone 1 is attached to the stirrer shaft 6 above the culture suspension.
  • the lower end dips into the culture suspension in order to almost completely rule out foam formation.
  • the cone rotates with the stirrer shaft. Since the immersed stirrer more or less only has to prevent the cells from sinking, the stirrer shaft can be rotated slowly, thereby avoiding shear forces.
  • the suspension With a pump, inside or outside the reactor, the suspension is continuously pumped from the bottom space to the top of the cone. The suspension then runs in the form of a film over the
  • the reactor can be operated in the same way with a plurality of cones arranged one above the other, with the release of culture suspension from an upper to a lower cone surface being effected very simply by means of openings in the cone located above.

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  • Wood Science & Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un bioréacteur présentant au moins temporairement dans sa partie supérieure (4) une surface (1) inclinée en direction de la surface de la suspension de culture, ainsi qu'un élément servant à transporter la suspension de culture (2) sur cette surface (1). L'alimentation en gaz peut être réalisée uniquement dans la partie supérieure (4), notamment à l'interface entre la partie supérieure (4) et le fond (3) contenant la suspension de culture.
PCT/IB1996/000157 1995-03-03 1996-03-01 Bioreacteur a surface agrandie Ceased WO1996027656A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH61795 1995-03-03
CH617/95-6 1995-03-03

Publications (1)

Publication Number Publication Date
WO1996027656A1 true WO1996027656A1 (fr) 1996-09-12

Family

ID=4191181

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB1996/000157 Ceased WO1996027656A1 (fr) 1995-03-03 1996-03-01 Bioreacteur a surface agrandie

Country Status (1)

Country Link
WO (1) WO1996027656A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4400575A1 (fr) * 2023-01-13 2024-07-17 MTM Anlagenbau GmbH Installation de prétraitement de matières premières solides pour la production de biogaz, installation de biogaz et procédé de production de biogaz

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2542031A (en) * 1947-09-12 1951-02-20 Humfeld Harry Fermentor for submerged cultures
US3262252A (en) * 1961-07-17 1966-07-26 Ebner Heinrich Apparatus for separating gas from foam
US4717669A (en) * 1986-08-18 1988-01-05 Vaclav Feres Centrifugal film fermenter
US5248613A (en) * 1991-07-08 1993-09-28 Roubicek Rudolf V Nonhomogeneous centrifugal film bioreactor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2542031A (en) * 1947-09-12 1951-02-20 Humfeld Harry Fermentor for submerged cultures
US3262252A (en) * 1961-07-17 1966-07-26 Ebner Heinrich Apparatus for separating gas from foam
US4717669A (en) * 1986-08-18 1988-01-05 Vaclav Feres Centrifugal film fermenter
US5248613A (en) * 1991-07-08 1993-09-28 Roubicek Rudolf V Nonhomogeneous centrifugal film bioreactor

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4400575A1 (fr) * 2023-01-13 2024-07-17 MTM Anlagenbau GmbH Installation de prétraitement de matières premières solides pour la production de biogaz, installation de biogaz et procédé de production de biogaz
WO2024149533A1 (fr) * 2023-01-13 2024-07-18 Mtm Anlagenbau Gmbh Système de prétraitement de matières premières solides pour la production de biogaz, système de production de biogaz et procédé de production de biogaz

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