WO2014191947A1 - Bioreactor for obtaining secondary plant constituents - Google Patents

Bioreactor for obtaining secondary plant constituents Download PDF

Info

Publication number
WO2014191947A1
WO2014191947A1 PCT/IB2014/061804 IB2014061804W WO2014191947A1 WO 2014191947 A1 WO2014191947 A1 WO 2014191947A1 IB 2014061804 W IB2014061804 W IB 2014061804W WO 2014191947 A1 WO2014191947 A1 WO 2014191947A1
Authority
WO
WIPO (PCT)
Prior art keywords
bioreactor
support plate
outlet
dimensionally stable
plates
Prior art date
Application number
PCT/IB2014/061804
Other languages
German (de)
French (fr)
Inventor
Alicia IDOUX
Philipp STEIGER
Jost Harr
Original Assignee
Rootec Bioactives Ag
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Rootec Bioactives Ag filed Critical Rootec Bioactives Ag
Publication of WO2014191947A1 publication Critical patent/WO2014191947A1/en

Links

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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of 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
    • C12M21/00—Bioreactors or fermenters specially adapted for specific uses
    • C12M21/14—Bioreactors or fermenters specially adapted for specific uses for producing enzymes
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/14—Bags
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/26—Constructional details, e.g. recesses, hinges flexible
    • 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
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/02—Membranes; Filters
    • 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
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/06—Plates; Walls; Drawers; Multilayer plates
    • 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
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/06—Nozzles; Sprayers; Spargers; Diffusers

Definitions

  • the present invention relates to a bioreactor for obtaining secondary plant constituents according to the preamble of patent claim 1.
  • the present invention is an improved device according to the prior art described in DE 100 16 554 A1.
  • the scale-up of a small plant is difficult because the inhomogeneous and non-intermixable tissue cultures in larger plants make the supply of nutrient solution difficult. Effort and risk of a scale-up are very high. In addition, you are no longer flexible with larger systems. Therefore, the method detailed in WO03029444A2 is advantageously performed by means of a plurality of relatively small bioreactors.
  • the vertically arranged carrier plates favor the vertical flow in the bioreactor. Although the nutrient solution / gas mixture is introduced horizontally, too many parts of the nutrient solution go directly down without nourishing the organ cultures located on the carrier plates. As a result, many circuits are needed to provide the plants with nutrients.
  • the centrally or peripherally arranged in the intermediate adapters spray nozzles allow the introduction of nutrient solution / gas mixture at the same place and in the same direction.
  • the organ cultures are thereby partially wetted excessively, which hinders the growth of the same.
  • organ cultures settled on the lower support plates are massively submerged by dripping from the upper support plates, which additionally hampers their growth.
  • the present invention now has the task of a bioreactor for the production of secondary Plant ingredients of the type mentioned above to improve such that a gleichschreibigere distribution of the sprayed nutrient solution allows better growth of the organ cultures and thus the
  • FIG. 4 Basic plan view of carrier plate
  • FIG. 5 top view of carrier plate a
  • FIG. 6 top view of carrier plate b
  • FIG. 7 top view of carrier plate c
  • FIG. 9 top view of carrier plate x
  • the presented invention has been developed. It differs significantly from known constructions.
  • the shape and arrangement of the carrier plates 30 were designed in connection with the spraying angle of the nutrient / gas mixture via the spray nozzles 11 by means of numerical fluid dynamics (CFD computational fluid dynamics) in order to ensure the most uniform possible supply of all organ cultures settled in the bioreactor.
  • CFD computational fluid dynamics numerical fluid dynamics
  • the dimensionally stable Deekel 10 forms together with the flexible sheath 2 and the dimensionally stable bottom 20, the vessel.
  • the support plates 30a ⁇ 30x are suspended within this vessel by means of a suspension 31 on the cover 10.
  • the suspension 31 consists of at least three flexible threads of sufficient strength to soft support plates 30a ⁇ 3öx are attached.
  • the volume of this bioactivator. X can be reduced to one fifth with all content through connection and denting at least (Fig 10-12, "Twist Bückling Principe" after Hunt, G.
  • FIG. 10 shows the Fa.ltpr.inzip on bioreactor 1 is shown.
  • Fig. 11 shows in detail the principle according to which the wrong field is the solid one. Draw lines that are folded outwards and the broken lines that fold inwards. Show lines.
  • FIG. 12 shows the geometric principle of folding, which is carried out according to this formula.
  • bioreactors 1 are delivered and stored sterile until unfolded for use.
  • the support plates 30 (FIGS. 3-7) have the same outer diameter 34. From this outer diameter 34 to the central bores 33a-33x, they are conical (FIG. 3), so that the central bores 33a-33x are always deeper than the outer diameters 34. Reason for this is the intended flow of liquid over the circle segments 32a-32x towards the center. In the center, the liquid then drips off through the central bores 33a-33x.
  • the central bore 33b of the support plate 30b is larger than the central bore 33a of the overlying support plate 30a. This regularity continues until the central bore 33x of the support plate 30x, which has the largest diameter. Therefore, the liquid carrying the nutrient and the desired metabolic product drips off without wetting or dripping onto the organ cultures located on the underlying support plate.
  • the carrier plates 30a-30x all have the same outer diameter 34. All support plates 30a-30x are connected to the suspension 31 at at least three points. This suspension 31 is made of flexible threads of adequate strength and is dimensionally stable Lid 10 attached. The support plates 30a-30x are suspended in the bioreactor, with the lowermost support plate 30x not touching the dimensionally stable base 20.
  • the size, configuration and orientation of the circle segments 32a-32x and the inlet angle of the spray nozzles 11 were determined by means of numerical flow simulation (CFD). One of the found arrangements is visible in FIG. Experiments have shown that the inventive design works much more efficiently and thus the yield is higher when the nutrient / gas mixture is sprayed into the bioreactor 1 in a kind of spiral mist. It has also been shown that the inlet via three spray nozzles 11 at an angle of 30-60 °, preferably 40-50 ° degrees is optimal.
  • the circle segments 32a of the top carrier plate 30a occupy the smallest and the circle segments 32x of the carrier plate 30x the largest proportion of the circular area.
  • the findings from development experiments have shown: If the proportion of the surface which give the organ cultures stop at the beginning of the process in the top support plate 30a is kept small and increases over the underlying support plates 30b - 30d to the bottom support plate 30x achieved the best yield.
  • the bottom 20 is inclined towards the outlet 21, so that the liquid always collects in the vicinity of the outlet 21.

Abstract

A bioreactor 1 for obtaining secondary plant constituents is presented. This consists of a flexible shell 2 in the form of a bag, closed at the top by a dimensionally stable lid 10 and at the bottom by a dimensionally stable base 20. In the interior, within the shell 2, at least one fixed carrier plate 30 is arranged in a freely suspended manner by means of a mounting assembly 31 secured to the lid (10). The bioreactor 1 can be charged with nutrients and gases via spray nozzles 11 in the lid 10. An outlet 21 in the base 20 is provided for the outflow of the remaining nutrient liquid and the desired metabolic product. The bioreactor 1 can be folded up together with the entire contents.

Description

Bioreaktor zur Gewinnung sekundärerBioreactor for obtaining secondary
Pflanzeninhaltsstoffen Plant ingredients
Die vorliegende Erfindung betrifft einen Bioreaktor zur Gewinnung sekundärer Pflanzeninhaltsstoffen gemäss Oberbegriff des Patentanspruchs 1. The present invention relates to a bioreactor for obtaining secondary plant constituents according to the preamble of patent claim 1.
Gegenstand der vorliegenden Erfindung ist eine verbesserte Vorrichtung nach dem in DE 100 16 554 A1 dargestellten Stand der Technik. Das Scale-up einer kleinen Anlage ist schwierig, da die inhomogenen und nicht zu durchmischenden Gewebekulturen in grösseren Anlagen die Versorgung mit Nährstofflösung erschweren. Aufwand und Risiko eines Scale-up sind sehr gross. Zudem ist man mit grösseren Anlagen nicht mehr flexibel. Deshalb wird das in WO03029444A2 detailliert beschriebene Verfahren mit Vorteil mittels einer Vielzahl relativ kleiner Bioreaktoren durchgeführt.  The present invention is an improved device according to the prior art described in DE 100 16 554 A1. The scale-up of a small plant is difficult because the inhomogeneous and non-intermixable tissue cultures in larger plants make the supply of nutrient solution difficult. Effort and risk of a scale-up are very high. In addition, you are no longer flexible with larger systems. Therefore, the method detailed in WO03029444A2 is advantageously performed by means of a plurality of relatively small bioreactors.
Die Praxis hat gezeigt, dass die Durchführung des Prozesses mit der in obiger Anmeldung vorgestellten Vorrichtung teuer ist und den gewünschten Prozess nicht effizient ablaufen lässt. So ist z.B. der Zeitaufwand nach jedem Einsatz sehr gross. Die Vorrichtung muss demontiert, gereinigt und in einem Autoklaven entkeimt werden, damit das Gerät für den erneuten Einsatz bereit ist. Da aus oben beschriebenen Gründen eine Vielzahl solcher Vorrichtungen im Einsatz sind, steht der Aufwand in keinem Verhältnis zum Ertrag. Das vorgestellte Verfahren wird mangels Wirtschaftlichkeit der bekannten Vorrichtung deshalb bis heute nicht eingesetzt. Practice has shown that carrying out the process with the device presented in the above application is expensive and does not efficiently run the desired process. For example, the time required after each use is very large. The device must be disassembled, cleaned and sterilized in an autoclave so that the device is ready for reuse. Since a plurality of such devices are in use for reasons described above, the effort is out of proportion to the yield. The proposed method is therefore not used for reasons of economy of the known device until today.
Die in DE 100 16 554 A1 vorgestellte Vorrichtung ist die Basis der vorliegenden Erfindung, sie weist aber für die Effizienz des Verfahrens nachteilige Eigenschaften auf: The device presented in DE 100 16 554 A1 forms the basis of the present invention, but it has disadvantageous properties for the efficiency of the method:
Die Vertikal angeordneten Trägerplatten begünstigen den vertikalen Strom im Bioreaktor. Obwohl das Nährstofflösung/Gasgemisch horizontal eingebracht wird, gehen zu viele Teile der Nährstofflösung direkt nach unten, ohne die auf den Trägerplatten angesiedelten Organkulturen zu nähren. Dies hat zur Folge, dass viele Kreisläufe notwendig sind, um die Pflanzen mit Nährstoff zu versorgen.  The vertically arranged carrier plates favor the vertical flow in the bioreactor. Although the nutrient solution / gas mixture is introduced horizontally, too many parts of the nutrient solution go directly down without nourishing the organ cultures located on the carrier plates. As a result, many circuits are needed to provide the plants with nutrients.
Die in den Zwischenadaptern zentral oder peripher angeordneten Sprühdüsen ermöglichen das Einbringen Nährstofflösung/Gasgemisch an gleichen Stellen und in gleicher Richtung. Die Organkulturen werden dadurch stellenweise übermässig benetzt, was das Wachstum derselben behindert .  The centrally or peripherally arranged in the intermediate adapters spray nozzles allow the introduction of nutrient solution / gas mixture at the same place and in the same direction. The organ cultures are thereby partially wetted excessively, which hinders the growth of the same.
Ferner werden die auf den unteren Trägerplatten angesiedelten Organkulturen durch das Abtropfen von den oberen Trägerplatten massiv übernetzt, was deren Wachstum zusätzlich behindert.  Furthermore, the organ cultures settled on the lower support plates are massively submerged by dripping from the upper support plates, which additionally hampers their growth.
Die vorliegende Erfindung stellt sich nunmehr die Aufgabe, einen Bioreaktor zur Gewinnung sekundärer Pflanzeninhaltsstoffen der eingangs genannten Art derart zu verbessern, dass eine gleichmassigere Verteilung der versprühten Nährstofflösung ein besseres Wachstum der Organkulturen ermöglicht und damit dieThe present invention now has the task of a bioreactor for the production of secondary Plant ingredients of the type mentioned above to improve such that a gleichmaßigere distribution of the sprayed nutrient solution allows better growth of the organ cultures and thus the
Wirtschaftlichkeit verbessert.. Profitability improved ..
Diese Aufgabe löst ein Bioreaktor mit den Merkmalen des Patentanspruches 1. Weitere Merkmale undThis object is achieved by a bioreactor with the features of claim 1. Further features and
Ausführungsbeispiele gehen aus den abhängigen Ansprüchen hervor und deren Vorteile sind in der nachfolgenden Beschreibung erläutert . Embodiments will become apparent from the dependent claims and the advantages thereof are explained in the following description.
In der Zeichnung zeigt : In the drawing shows:
Fig 1 Bioreaktor Fig 1 bioreactor
Fig 2 Boden, Trägerplatten und Deckel Fig 2 bottom, support plates and lid
Fig 3 Prinzipielle Seitenansicht Trägerplatte Fig. 3 Basic side view of carrier plate
Fig 4 Prinzipielle Aufsicht Trägerplatte FIG. 4 Basic plan view of carrier plate
Fig 5 Aufsicht Trägerplatte a FIG. 5, top view of carrier plate a
Fig 6 Aufsicht Trägerplatte b FIG. 6, top view of carrier plate b
Fig 7 Aufsicht Trägerplatte c FIG. 7, top view of carrier plate c
Fig 8 Aufsicht Trägerplatte d Fig 8 supervision carrier plate d
Fig 9 Aufsicht Trägerplatte x FIG. 9, top view of carrier plate x
Fig 10 FaltSystem am Bioreaktor Fig 10 Folding system on the bioreactor
Fig 11 Faltlinien Fig 11 fold lines
Fig 12 Faltgeometrie Fig 12 Faltgeometrie
Die Figuren stellen mögliche Ausführungsbeispiele dar, welche in der nachfolgenden Beschreibung erläutert werden . Die Kultivierung von Zellen zur Herstellung von Zellmaterial, insbesondere von metabolischen Produkten dieser Zellen gewinnt an Bedeutung. Die chemische Synthese solcher Produkte ist häufig unwirtschaftlich, schwierig oder gar unmöglich. Für pflanzliche Organkulturen [transformierte Wurzelhaar- (Hairy root) , Wurzel- oder Sprosskulturen (shooty teratomas)] bedarf es spezieller Vorrichtungen. Die Grundlagen für solche Geräte sind in DE 100 16 554 A1 offenbart. The figures represent possible embodiments, which will be explained in the following description. The cultivation of cells for the production of cell material, in particular of the metabolic products of these cells is becoming more important. The chemical synthesis of such products is often uneconomical, difficult or even impossible. For plant organ cultures [transformed root hair (Hairy root), root or shoot shooty (shooty teratomas)] requires special devices. The basics for such devices are disclosed in DE 100 16 554 A1.
Um den Prozess im Bioreaktor 1 (Fig 1) effizienter und damit wirtschaftlicher zu machen, wurde die vorgestellte Erfindung entwickelt. Sie unterscheidet sich massgeblich von bekannten Konstruktionen. Form und Anordnung der Trägerplatten 30 wurden im Zusammenhang mit dem Einsprühwinkel der Nährstoff/Gasmischung über die Sprühdüsen 11 mittels numerischer Strömungssimulation (CFD computational fluid dynamics) ausgelegt, um eine möglichst gleichmässige Versorgung aller im Bioreaktor angesiedelten Organkulturen zu gewährleisten. In order to make the process in the bioreactor 1 (FIG. 1) more efficient and therefore more economical, the presented invention has been developed. It differs significantly from known constructions. The shape and arrangement of the carrier plates 30 were designed in connection with the spraying angle of the nutrient / gas mixture via the spray nozzles 11 by means of numerical fluid dynamics (CFD computational fluid dynamics) in order to ensure the most uniform possible supply of all organ cultures settled in the bioreactor.
Im Laborversuch und in den Berechnungen wurden fünf Trägerplatten 30a-x eingesetzt, weshalb beispielhaft die Anordnung mit fünf Trägerplatten 30a-x beschrieben wird. Je nach Anwendung können jedoch weniger oder mehr Trägerplatten eingesetzt werden. Der formstabile Deekel 10 bildet zusammen mit der flexiblen Hülle 2 und dem formstabilen Boden 20 das Gefäss. Die Trägerplatten 30a~30x sind innerhalb dieses Gefässes mittels einer Aufhängung 31 am Deckel 10 eingehängt. Die Aufhängung 31 besteht aus mindestens drei flexiblen Fäden genügender Festigkeit an weichen die Trägerplatten 30a~3öx befestigt sind. Das Volumen dieses Bioiraktors. X, kann, mit allem Inhalt durch Verbindung und Einbeulung auf mindesetens einen Fünftel reduziert werden (Fig 10-12, „Twist Bückling Principe" nach Hunt,G. and Ario, I (2004) „Twist buckling and the foldable cylinder: an exercise in Origami". International Journal of Non-Linear Mechanics, 40(6), p.833-843) . In. Fig 10 wird das Fa.ltpr.inzip am Bioreaktor 1 gezeigt . In Fig 11 zeigt im Detail das Prinzip, wonach die irrt Fai.thereich die ausgezogenen. Striche die nach aussen gefalteten und die unterbrochenen Striche die nach innen gefalteten. Linien zeigen. Die Fig 12 zeigt das geometrische Prinzip der Faltung, welche nach dieser Formel vor sich geht.
Figure imgf000008_0001
Five support plates 30a-x were used in the laboratory experiment and in the calculations, which is why the arrangement with five support plates 30a-x is described by way of example. Depending on the application, however, fewer or more carrier plates can be used. The dimensionally stable Deekel 10 forms together with the flexible sheath 2 and the dimensionally stable bottom 20, the vessel. The support plates 30a ~ 30x are suspended within this vessel by means of a suspension 31 on the cover 10. The suspension 31 consists of at least three flexible threads of sufficient strength to soft support plates 30a ~ 3öx are attached. The volume of this bioactivator. X, can be reduced to one fifth with all content through connection and denting at least (Fig 10-12, "Twist Bückling Principe" after Hunt, G. and Ario, I (2004) "Twist buckling and the foldable cylinder: an exercise in Origami. "International Journal of Non-Linear Mechanics, 40 (6), p.833-843). In. 10 shows the Fa.ltpr.inzip on bioreactor 1 is shown. In Fig. 11 shows in detail the principle according to which the wrong field is the solid one. Draw lines that are folded outwards and the broken lines that fold inwards. Show lines. FIG. 12 shows the geometric principle of folding, which is carried out according to this formula.
Figure imgf000008_0001
Der Sinn dieses reglementierten Faltprozesses ist der Erhalt der Dichtheit der Hülle, auch nach dem für Lagerung und Transport wichtigen Falten und vor allem nach dem Entfalten. In zusammengefalteter Form werden die Bioreaktoren 1 nämlich steril geliefert und gelagert, bis sie für den Einsatz entfaltet werden. The purpose of this regulated folding process is to maintain the tightness of the envelope, even after the wrinkles that are important for storage and transport, and above all after unfolding. Namely, in a collapsed form, bioreactors 1 are delivered and stored sterile until unfolded for use.
Die Trägerplatten 30(Fig 3-7) haben denselben Aussendurchmesser 34. Von diesem Aussendurchmesser 34 zu den Zentralbohrungen 33a-33x sind sie konisch (Fig 3) , so dass die Zentralbohrungen 33a-33x immer tiefer liegen, als die Aussendurchmesser 34. Grund dafür ist der gewollte Ablauf der Flüssigkeit über die Kreissegmente 32a-32x hin zum Zentrum. Im Zentrum tropft die Flüssigkeit dann durch die Zentralbohrungen 33a-33x ab. Die Zentralbohrung 33b der Trägerplatte 30b grösser als die Zentralbohrung 33a der darüber liegenden Trägerplatte 30a. Diese Gesetzmässigkeit setzt sich fort bis zur Zentralbohrung 33x der Trägerplatte 30x, welche den grössten Duchmesser aufweist. Daher tropft die den Nährstoff und das erwünschte metabolische Produkt tragende Flüssigkeit ab, ohne die auf der darunter liegenden Trägerplatte angesiedelten Organkulturen zu benetzen oder darauf zu tropfen. The support plates 30 (FIGS. 3-7) have the same outer diameter 34. From this outer diameter 34 to the central bores 33a-33x, they are conical (FIG. 3), so that the central bores 33a-33x are always deeper than the outer diameters 34. Reason for this is the intended flow of liquid over the circle segments 32a-32x towards the center. In the center, the liquid then drips off through the central bores 33a-33x. The central bore 33b of the support plate 30b is larger than the central bore 33a of the overlying support plate 30a. This regularity continues until the central bore 33x of the support plate 30x, which has the largest diameter. Therefore, the liquid carrying the nutrient and the desired metabolic product drips off without wetting or dripping onto the organ cultures located on the underlying support plate.
Die Trägerplatten 30a-30x weisen alle denselben Aussendurchmesser 34 auf. Alle Trägerplatten 30a-30x sind an mindestens drei Punkten mit der Aufhängung 31 verbunden. Diese Aufhängung 31 besteht aus flexiblen Fäden angemessener Festigkeit und ist am formstabilen Deckel 10 befestigt. Die Trägerplatten 30a-30x hängen in den Bioreaktor, wobei die unterste Trägerplatte 30x den formstabilen Boden 20 nicht berührt. The carrier plates 30a-30x all have the same outer diameter 34. All support plates 30a-30x are connected to the suspension 31 at at least three points. This suspension 31 is made of flexible threads of adequate strength and is dimensionally stable Lid 10 attached. The support plates 30a-30x are suspended in the bioreactor, with the lowermost support plate 30x not touching the dimensionally stable base 20.
Grösse, Ausgestaltung und Orientierung der Kreissegmente 32a-32x und der Einlasswinkel der Sprühdüsen 11 wurden mittels numerischer Strömungssimulation (CFD) festgelegt. Eine der gefundenen Anordnungen ist in Fig 2 sichtbar. Versuche haben gezeigt, dass die erfindungsgemässe Auslegung viel effizienter arbeitet und dadurch die Ausbeute (yield) höher wird, wenn das Nährstoff/Gasgemisch in einer art Spiralnebel in den Bioreaktor 1 eingesprüht wird. Es hat sich auch gezeigt, dass der Einlass über drei Sprühdüsen 11 im Winkel von 30-60°, vorzugsweise 40-50° Grad optimal ist. The size, configuration and orientation of the circle segments 32a-32x and the inlet angle of the spray nozzles 11 were determined by means of numerical flow simulation (CFD). One of the found arrangements is visible in FIG. Experiments have shown that the inventive design works much more efficiently and thus the yield is higher when the nutrient / gas mixture is sprayed into the bioreactor 1 in a kind of spiral mist. It has also been shown that the inlet via three spray nozzles 11 at an angle of 30-60 °, preferably 40-50 ° degrees is optimal.
Die Kreissegmente 32a der obersten Trägerplatte 30a nehmen den kleinsten und die Kreissegmente 32x der Trägerplatte 30x den grössten Anteil der Kreisfläche ein. Die Erkenntnisse aus Entwicklungs-Versuchen haben gezeigt: Wenn der Anteil der Fläche, welche den Organkulturen zu Beginn des Prozesses Halt geben in der obersten Trägerplatte 30a klein gehalten wird und sich über die darunter liegenden Trägerplatten 30b - 30d bis zur untersten Trägerplatte 30x vergrössert, wird die beste Ausbeute erzielt. Der Boden 20 ist zum Auslass 21 hin geneigt, so dass sich die Flüssigkeit immer in der Nähe des Auslasses 21 sammelt. The circle segments 32a of the top carrier plate 30a occupy the smallest and the circle segments 32x of the carrier plate 30x the largest proportion of the circular area. The findings from development experiments have shown: If the proportion of the surface which give the organ cultures stop at the beginning of the process in the top support plate 30a is kept small and increases over the underlying support plates 30b - 30d to the bottom support plate 30x achieved the best yield. The bottom 20 is inclined towards the outlet 21, so that the liquid always collects in the vicinity of the outlet 21.

Claims

Patentansprüche claims
1. Bioreaktor (1) zur Gewinnung sekundärer Pflanzen- Inhaltsstoffen, bestehend aus einer beuteiförmigen, flexiblen Hülle (2) , welche oben durch einen formstabilen Deckel (10) abgeschlossen ist, wobei innerhalb der Hülle (2) mindestens eine feste Trägerplatte (30) in einer am Deckel (10) befestigten Aufhängung (31) hängend angeordnet ist und die so gebildete Vorrichtung Zu- und Abführungen für flüssige Nährstoffe und Gase aufweist, dadurch gekennzeichnet, dass der Bioreaktor (1) unten einen formstabilen Boden (20) aufweist und Deckel (10) , Hülle (2) und Boden (20) , mit den horizontal angeordneten Trägerplatten (30) und deren Aufhängung (31) , eine zusammenlegbare Vorrichtung bilden, wobei Hülle (2) , Deckel (10) und Boden (20) ein nur durch vorgesehene Ein- und Auslässe durchbrochenes, dichtes Gefäss bilden.  1. Bioreactor (1) for obtaining secondary plant ingredients, consisting of a bag-shaped, flexible sheath (2), which is closed at the top by a dimensionally stable cover (10), wherein within the sheath (2) at least one solid support plate (30) in a suspension (31) fastened to the cover (10) and the device thus formed has inlets and outlets for liquid nutrients and gases, characterized in that the bioreactor (1) has a dimensionally stable base (20) at the bottom and covers (10), shell (2) and bottom (20), with the horizontally disposed support plates (30) and their suspension (31) forming a collapsible device, wherein sheath (2), lid (10) and bottom (20) form only through openings and outlets openwork, dense vessel.
2. Vorrichtung gemäss Anspruch 1, dadurch gekennzeichnet, dass alle Trägerplatten (30a-30x) im Zentrum Zentral- Bohrungen (33a-33x) unterschiedlicher Dimension, aber Aussendurchmesser (34) gleicher Dimension aufweisen. 2. Device according to claim 1, characterized in that all support plates (30a-30x) in the center central bores (33a-33x) of different dimensions, but outer diameter (34) have the same dimension.
3. Vorrichtung gemäss Anspruch 2, dadurch gekennzeichnet, dass die Zentralbohrungen (33a-33x) mindestens 5mm tiefer liegen als die Aussendurchmesser (34) der Trägerplatten (30a-30x) . 3. A device according to claim 2, characterized in that the central bores (33a-33x) are at least 5mm lower than the outer diameter (34) of the carrier plates (30a-30x).
4. Vorrichtung gemäss Anspruch 2, dadurch gekennzeichnet, dass die Zentralbohrung (33a) der obersten Trägerplatte (30a) am kleinsten ist, und die Zentralbohrungen (33a-33x) im Durchmesser grösser werden, so dass die Zentralbohrung (33x) der Trägerplatte (30x) den grössten Durchmesser aufweist.4. The device according to claim 2, characterized in that the central bore (33 a) of the uppermost support plate (30 a) is smallest, and the central bores (33 a- 33 x) in diameter are larger, so that the central bore (33 x) of the support plate (30x ) has the largest diameter.
5. Vorrichtung gemäss Anspruch 1, dadurch gekennzeichnet, dass alle Trägerplatten (30a-30x) mindestens drei auf deren Umfang gleichmässig verteilte Kreissegmente (32a-32e) mit netzartiger Struktur aufweisen. 5. The device according to claim 1, characterized in that all carrier plates (30a-30x) have at least three circumferentially uniformly distributed circular segments (32a-32e) with reticulated structure.
6. Vorrichtung gemäss Anspruch 5, dadurch gekennzeichnet, dass die beanspruchte Fläche des Kreissegments (32a) der obersten Trägerplatte (30a) am kleinsten ist und die Flächen der Kreissegmente (32a-32x) grösser werden, so dass die unterste Trägerplatte (30x) die grösste Fläche aufweist.  6. The device according to claim 5, characterized in that the claimed surface of the circle segment (32 a) of the uppermost support plate (30 a) is smallest and the surfaces of the circle segments (32 a- 32 x) are larger, so that the lowermost support plate (30 x) the has the largest area.
7. Vorrichtung gemäss Anspruch 1, dadurch gekennzeichnet, dass sich der Boden (20) und die unterste Trägerplatte (30x) nicht berühren.  7. The device according to claim 1, characterized in that the bottom (20) and the bottom support plate (30x) do not touch.
8. Vorrichtung gemäss Anspruch 1, dadurch gekennzeichnet, dass der Boden (20) einen Auslass (21) aufweist, wobei der Boden (20) zu diesem Auslass (21) hin nach unten geneigt ist und der Auslass (21) am untersten Punkt des Bodens angeordnet ist.  Device according to claim 1, characterized in that the bottom (20) has an outlet (21), the bottom (20) being inclined downwards towards this outlet (21) and the outlet (21) at the lowest point of the Floor is arranged.
PCT/IB2014/061804 2013-05-30 2014-05-29 Bioreactor for obtaining secondary plant constituents WO2014191947A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH10342013A CH708178A2 (en) 2013-05-30 2013-05-30 Bioreactor for the extraction of phytochemicals.
CH01034/13 2013-05-30

Publications (1)

Publication Number Publication Date
WO2014191947A1 true WO2014191947A1 (en) 2014-12-04

Family

ID=51162856

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2014/061804 WO2014191947A1 (en) 2013-05-30 2014-05-29 Bioreactor for obtaining secondary plant constituents

Country Status (2)

Country Link
CH (1) CH708178A2 (en)
WO (1) WO2014191947A1 (en)

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2202549A (en) * 1987-03-20 1988-09-28 Philip John Whitney Foldable fermenter
US6254775B1 (en) * 1998-03-09 2001-07-03 Mcelvaney James D. Anaerobic digester system and method
DE10016554A1 (en) 2000-04-03 2001-10-18 Rootec Ges Fuer Bioaktive Wirk Plant or animal tissue cultivation unit, comprises fermenter container, supply for liquid nutrients and gases, discharger for used nutrients, and carrier plates
WO2003029444A2 (en) 2001-09-28 2003-04-10 Rootec Gesellschaft Für Bioaktive Wirkstoffe mbH Method and device for extracting secondary plant constituents
WO2006093572A2 (en) * 2005-03-02 2006-09-08 Hynetics, Llc Systems and methods for mixing and sparging solutions and/or suspensions
EP1854872A1 (en) * 2006-05-12 2007-11-14 Marcel Röll Reaction and culture vessel for microorganisms and cell culture
US20080118974A1 (en) * 2006-11-20 2008-05-22 Gregory Roger Martin Large scale cell culture vessel
WO2008088371A2 (en) * 2006-06-16 2008-07-24 Xcellerex, Inc. Gas delivery configurations, foam control systems, and bag molding methods and articles for collapsible bag vessels and bioreactors
WO2010042072A1 (en) * 2008-10-08 2010-04-15 Agency For Science, Technology And Research Apparatus for culturing anchorage dependent cells
US20110207218A1 (en) * 2010-02-22 2011-08-25 Hyclone Laboratories, Inc. Mixing system with condenser
WO2012112879A2 (en) * 2011-02-17 2012-08-23 Worcester Polytechnic Institute Plant and fungi micropropagation methods and products made thereby

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2202549A (en) * 1987-03-20 1988-09-28 Philip John Whitney Foldable fermenter
US6254775B1 (en) * 1998-03-09 2001-07-03 Mcelvaney James D. Anaerobic digester system and method
DE10016554A1 (en) 2000-04-03 2001-10-18 Rootec Ges Fuer Bioaktive Wirk Plant or animal tissue cultivation unit, comprises fermenter container, supply for liquid nutrients and gases, discharger for used nutrients, and carrier plates
WO2003029444A2 (en) 2001-09-28 2003-04-10 Rootec Gesellschaft Für Bioaktive Wirkstoffe mbH Method and device for extracting secondary plant constituents
WO2006093572A2 (en) * 2005-03-02 2006-09-08 Hynetics, Llc Systems and methods for mixing and sparging solutions and/or suspensions
EP1854872A1 (en) * 2006-05-12 2007-11-14 Marcel Röll Reaction and culture vessel for microorganisms and cell culture
WO2008088371A2 (en) * 2006-06-16 2008-07-24 Xcellerex, Inc. Gas delivery configurations, foam control systems, and bag molding methods and articles for collapsible bag vessels and bioreactors
US20080118974A1 (en) * 2006-11-20 2008-05-22 Gregory Roger Martin Large scale cell culture vessel
WO2010042072A1 (en) * 2008-10-08 2010-04-15 Agency For Science, Technology And Research Apparatus for culturing anchorage dependent cells
US20110207218A1 (en) * 2010-02-22 2011-08-25 Hyclone Laboratories, Inc. Mixing system with condenser
WO2012112879A2 (en) * 2011-02-17 2012-08-23 Worcester Polytechnic Institute Plant and fungi micropropagation methods and products made thereby

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Twist Bückling Principe'' nach Hunt, G. and Ario, I (2004) ''Twist buckling and the foldable cylinder: an exercise in Origami", INTERNATIONAL JOURNAL OF NON-LINEAR MECHANICS, vol. 40, no. 6, pages 833 - 843

Also Published As

Publication number Publication date
CH708178A2 (en) 2014-12-15

Similar Documents

Publication Publication Date Title
EP1465977B1 (en) Device for raising or cultivating cells in a container-like receptacle
EP2084260A1 (en) Method and device for aeration, particularly for microbiological fermentation and for cell cultivation
DE1657280C3 (en)
DE102006002836A1 (en) Introduction of biogas into a fermenter
DE1457065A1 (en) Method and device for stirring and for generating a circulation in amounts of liquid
DE10016554A1 (en) Plant or animal tissue cultivation unit, comprises fermenter container, supply for liquid nutrients and gases, discharger for used nutrients, and carrier plates
DE3818776A1 (en) Process for the cultivation of cells in a fermenter, and fermenter intended for carrying out the process
DE112018000045T5 (en) Interior component, fluidized bed reactor and process for producing trichlorosilane
WO2014191947A1 (en) Bioreactor for obtaining secondary plant constituents
CH677616A5 (en)
EP0365621B1 (en) Device for submerged culture of tissue cells
DE546074C (en) Device for the fermentation of organic substances
EP1736419B1 (en) Disposable container
EP0021257B1 (en) Process for surface growing of nucleus-containing cells and production of cell culture-dependent products
DE19800875A1 (en) Manufacture of aerogel(s) by transfer of lyogel formed in portable vessel
DE10210908A1 (en) Device for applying liquid media and method therefor
EP0075687A2 (en) Vacuum filtration bench
DE3900727A1 (en) METHOD AND DEVICE FOR PURIFYING WASTEWATER OR EXHAUST GAS
DE102005002938B4 (en) Method for supplying cells or tissues
DE202005009425U1 (en) Device for culturing cells in a vessel, useful e.g. for preparation of antibodies, comprising an oscillatory stirrer, membrane basket, containing carrier, and gasification membrane on the outside of the basket
EP0965632B1 (en) Continuous fermentation system
DE2539453A1 (en) METHOD FOR IMPLEMENTING A MICROBIOLOGICAL SUBSTRATE AND DEVICE FOR IMPLEMENTING THE METHOD
DE3614712C2 (en)
DE202018106835U1 (en) Plant pot with irrigation system
DE1933493A1 (en) Reaction container for chemical reactions

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14736974

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14736974

Country of ref document: EP

Kind code of ref document: A1