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WO2008107518A1 - Bioreactor - Google Patents

Bioreactor Download PDF

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Publication number
WO2008107518A1
WO2008107518A1 PCT/FI2008/050102 FI2008050102W WO2008107518A1 WO 2008107518 A1 WO2008107518 A1 WO 2008107518A1 FI 2008050102 W FI2008050102 W FI 2008050102W WO 2008107518 A1 WO2008107518 A1 WO 2008107518A1
Authority
WO
WIPO (PCT)
Prior art keywords
mass
bioreactor
heat exchanger
conveyor
reactor tank
Prior art date
Application number
PCT/FI2008/050102
Other languages
English (en)
French (fr)
Inventor
Tuomas Mattila
Seppo JÄÄSKELÄINEN
Veera Virtanen
Ulla Moilanen
Erika Winquist
Original Assignee
Teknillinen Korkeakoulu
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 Teknillinen Korkeakoulu filed Critical Teknillinen Korkeakoulu
Publication of WO2008107518A1 publication Critical patent/WO2008107518A1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • C12M41/18Heat exchange systems, e.g. heat jackets or outer envelopes
    • C12M41/24Heat exchange systems, e.g. heat jackets or outer envelopes inside the vessel
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/02Apparatus for enzymology or microbiology with agitation means; with heat exchange means
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/16Apparatus for enzymology or microbiology containing, or adapted to contain, solid media
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M27/00Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/02Stirrer or mobile mixing elements
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M39/00Means for cleaning the apparatus or avoiding unwanted deposits of microorganisms

Definitions

  • the invention relates to a bioreactor designed for processing solid and/or high- viscosity mass and provided with a vertical reactor tank.
  • the invention also relates to a method for manufacturing and using said bioreactor.
  • bioreactors When processing solid and/or high-viscosity mass bioreactors, the problem often is that the heating or cooling of the mass cannot be realized in an even way.
  • bioreactors can contain unmixed spots that are not in contact with the heat transfer surfaces.
  • Attempts have been made to solve the problem by providing the bioreactor with an inner mixer that in practice covers the whole volume of the reactor.
  • nNauta mixers As alternative solutions, for example nNauta mixers have been used.
  • the inner instrumentation of this kind of bioreactor is cumbersome, and it is not suited for all masses.
  • a n ⁇ Jauta mixer causes fairly high torque forces in the supporting structures, in which case the manufacturing expenses become high owing to the specific structure.
  • a bioreactor according to the invention is vertical, and inside its reactor tank, spaced apart from the inner wall surfaces and ceiling of the reactor tank, there is arranged a vertical cylindrical heat exchanger.
  • a vertical cylindrical heat exchanger Inside the heat exchanger, there is provided an upwardly and/or downwardly conveying mass conveyor, such as a screw conveyor.
  • the low point of the heat exchanger is located in the vicinity of the low point of the mass conveyor, for instance immediately underneath it, for conveying mass into the heat exchanger and out of it.
  • the mass to be processed can be fed, via the intermediate space located in between the heat exchanger and the reactor tank, into the heat exchanger, whereafter the mass conveyor conveys the mass upwardly along the heat transfer surface.
  • the heat transfer is particularly efficient, because the whole of the mass is effectively conveyed through the heat exchanger.
  • a high degree of mass circulation is obtained in the reactor.
  • the mass is transferred from the output end of the heat exchanger via an intermediate space left outside the heat exchanger to the input end of the heat exchanger.
  • the proceeding of the mass in the intermediate space is carried out downwardly from the top due to gravity.
  • the mass proceeding downwardly in the intermediate space is at least partly in contact with the heat exchanger surfaces, in which case the heat transfer becomes even more efficient.
  • the conveying of the mass is carried out efficiently, because the mass conveyor of the equipment can function also when the bioreactor is fairly empty.
  • the mass conveyor conveys the mass effectively upwards in the interior of the heat exchanger. In the intermediate space, the upwardly conveyed mass again drops on the bottom.
  • a bioreactor there can effectively be processed for example mass with a dry matter content of 10-100%, such as 25-40%.
  • a screw conveyor is particularly well suited for conveying this kind of mass, because it is capable of conveying particularly solid mass or mass wit a high viscosity.
  • a screw conveyor also improves the mass heat transfer, while mixing the mass both in the vertical and horizontal directions.
  • a paddle conveyor can be used.
  • the size of the bioreactor can vary depending on the embodiment in question. It can be realized as a laboratory-scale or pilot-scale equipment, or as a large-scale production equipment.
  • a reactor according to the invention can be used for example in extraction, where the dry matter content is only about 12%. On the other hand, also completely dry mass can be technically processed in the reactor.
  • a bioreactor according to the invention is technically advantageous, because there is provided ample installation space for them. Because the mixer and the heat exchanger are permanently installed, the placing of sensors, transmitters etc. inside the bioreactor is carried out simply and with low expenses.
  • This kind of bioreactor is advantageous also because the necessary inoculation conduit/conduits and mass feed conduit/conduits can easily be connected to the bioreactor.
  • the mass conveyor can be made such that for example only one lead- through in the lid is required in the bioreactor.
  • the bioreactor can easily be provided with several lead-throughs for example for sensors.
  • the circumferential speed of the mass conveyor in the vicinity of the heat exchanger surface, is 0.05-0.5 m/s, such as 0.1-0.25 m/s.
  • the circumferential speed of the mass conveyor can be adjusted, in which case the bioreactor can process even largely different masses.
  • the bioreactor also includes an exterior heat exchanger, such as a heat exchanger jacket.
  • an exterior heat exchanger such as a heat exchanger jacket.
  • the cross-sectional diameter of the interior of the cylindrical heat exchanger is 20-70% of the diameter of the reactor tank, such as 30-60% of the diameter of the reactor tank. It is possible to manufacture for example a bioreactor where the diameter of the interior of the heat exchanger is 40-50% of the reactor tank diameter.
  • the term diameter refers to a horizontal cross-sectional diameter.
  • the cross-sectional surface area of the heat exchanger with respect to its height can vary depending on the embodiment in question. It can be constant, upwardly widening or upwardly narrowing.
  • the conveying of the mass can be affected by means of the design. For example, there can be manufactured a bioreactor where the share of the intermediate space in the lower part of the bioreactor is relatively small, in which case the conveying of the mass to the mass conveyor is made more effective.
  • the cross-section of a cylindrical heat exchanger can advantageously be circular in shape. As regards the cross- sectional mixing surface of the mass conveyor, it is preferably symmetrical.
  • the ratio of the diameters of the mass conveyor and the heat exchanger can vary in different embodiments.
  • the size of the clearance left between the mass conveyor and the heat exchanger depends for example on the solids content and structure of the mass. According to an embodiment of the invention, the diameter of the mass conveyor is 90-100%, for instance 94-98%, of the diameter of the heat exchanger.
  • This kind of mass conveyor effectively conveys many types of mass inside the heat exchanger from the lower part to the upper part thereof. This is particularly useful for example when the degree of filling in the bioreactor is low, for instance in the final stages of cultivation.
  • the mass conveyor also serves as a mass mixer, such as a paddle mixer or a screw mixer. This further improves the mixing and heat transfer of the mass, because the mass to be processed is distributed more evenly and more efficiently on the heat transfer surface of the heat exchanger.
  • a mass mixer such as a paddle mixer or a screw mixer.
  • the proceeding direction of the mass conveyor can be changed from upwardly conveying to downwardly conveying.
  • This kind of mass conveyor can advantageously be used as a mass remover in a bioreactor, by providing a mass removal conduit in the lower part of the bioreactor, for instance in its bottom or its lower wall. This is particularly advantageous when processing in the bioreactor masses that are difficult to transfer.
  • the bioreactor advantageously for instance at the lower end of the mass conveyor, there are arranged guide elements for guiding the mass to be processed to the heat exchanger. This improves the mixing of the mass to be processed, as well as the proceeding of the mass from the intermediate space to the heat exchanger, thus further improving the heat transfer of the mass.
  • the bioreactor is provided with scrapers, such as a bottom scraper and/or a wall scraper, for guiding the mass to be processed to the mass conveyor.
  • scrapers such as a bottom scraper and/or a wall scraper
  • the scraper is connected to the mass conveyor.
  • in the reactor tank, underneath the screw mixer there is arranged an intermediate bottom that is at least partly permeable to water and air. This makes the operation of the equipment even more versatile and in part affects the properties of the mass and thereby also the heat exchange and mixing.
  • the moisture in the mass to be processed is transferred, via the intermediate bottom, to a separate lower space, from where it can be further removed through a separate conduit.
  • a gas pipework for conducting air and/or steam into the reactor tank.
  • the conduit provided in the lower part of the bioreactor is a liquid conduit, such as a condensate removal conduit. It can be used for example for removing condensate applied in sterilization and/or for removing excess moisture separated from the mass.
  • the bioreactor is provided with an intermediate bottom, underneath which there is arranged a gas pipework for conducting air and/or steam into the reactor tank, and a condensate removal conduit for removing the condensate of the steam applied in sterilization and/or excess moisture separated from the mass.
  • the bioreactor is provided with an inoculation conduit for increasing the inoculate.
  • an inoculation conduit for increasing the inoculate.
  • it is located in the upper part of the bioreactor, so that the inoculate is distributed evenly in the whole volume of the mass.
  • the bioreactor is provided with a sampling conduit and/or a feed aperture in the housing.
  • the sampling conduit also serves as the housing feed aperture.
  • the heat exchanger is a water heat exchanger. In certain applications, this kind of arrangement is particularly advantageous both technically and economically. Detailed description of the invention
  • Figure 1 illustrates a cross-section of an embodiment of a bioreactor.
  • Figure 1 illustrates a bioreactor, inside which there is arranged, spaced apart from inner wall surfaces and ceiling of the reactor tank, a vertical cylindrical heat exchanger 2, inside which there is provided a vertical mass conveyor 1 , and the low point of the mass conveyor 1 is located immediately underneath the low point of the heat exchanger 2 for conveying mass into the heat exchanger 2 and out of it.
  • guide elements 3 At the lower end of the mass conveyor, there are arranged guide elements 3 for guiding the mass to be mixed to the mass conveyor/from mass conveyor 1.
  • Figure 1 also illustrates an intermediate bottom 4 arranged in the lower part of the bioreactor, underneath which intermediate bottom 4 there is located an air feed pipework 5 and a condensate removal conduit 6.
  • the total height of the laboratory-scale bioreactor illustrated in Figure 1 is about 40 cm, and its outer diameter is about 25 cm.
  • the height of the heat exchanger is 19 cm, its outer diameter is about 14 cm and its inner diameter is about 11 cm.
  • Said reactor was used for processing for example oat husk mass with a dry matter content of 33%. At the initial stage, the reactor was filled with mass, so that its height was about 30 cm, and during the cultivation, the mass height in the intermediate space can be reduced for example down to 15 cm.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Sustainable Development (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Thermal Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Paper (AREA)
PCT/FI2008/050102 2007-03-05 2008-03-04 Bioreactor WO2008107518A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FI20070190A FI120738B (fi) 2007-03-05 2007-03-05 Bioreaktori
FI20070190 2007-03-05

Publications (1)

Publication Number Publication Date
WO2008107518A1 true WO2008107518A1 (en) 2008-09-12

Family

ID=37929995

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/FI2008/050102 WO2008107518A1 (en) 2007-03-05 2008-03-04 Bioreactor

Country Status (2)

Country Link
FI (1) FI120738B (fi)
WO (1) WO2008107518A1 (fi)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014175723A2 (en) 2013-04-24 2014-10-30 Universiti Kebangsaan Malaysia A bioreactor

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US285736A (en) * 1883-09-25 william dopp
US3977946A (en) * 1975-01-24 1976-08-31 Phillips Petroleum Company Fermentation apparatus
US3986934A (en) * 1973-08-30 1976-10-19 Mueller Hans Apparatus for aerobic cultivation of micro-organisms
US4717669A (en) * 1986-08-18 1988-01-05 Vaclav Feres Centrifugal film fermenter
WO1992004114A1 (en) * 1990-09-04 1992-03-19 Reanal Finomvegyszergyár Apparatus for creating intensive contact between a liquid and a particulate solid
KR100311057B1 (ko) * 1998-04-06 2002-04-22 손재익 내부순환형광생물반응기및이를이용한광합성미생물의배양방법

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US285736A (en) * 1883-09-25 william dopp
US3986934A (en) * 1973-08-30 1976-10-19 Mueller Hans Apparatus for aerobic cultivation of micro-organisms
US3977946A (en) * 1975-01-24 1976-08-31 Phillips Petroleum Company Fermentation apparatus
US4717669A (en) * 1986-08-18 1988-01-05 Vaclav Feres Centrifugal film fermenter
WO1992004114A1 (en) * 1990-09-04 1992-03-19 Reanal Finomvegyszergyár Apparatus for creating intensive contact between a liquid and a particulate solid
KR100311057B1 (ko) * 1998-04-06 2002-04-22 손재익 내부순환형광생물반응기및이를이용한광합성미생물의배양방법

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014175723A2 (en) 2013-04-24 2014-10-30 Universiti Kebangsaan Malaysia A bioreactor

Also Published As

Publication number Publication date
FI20070190A (fi) 2008-09-06
FI20070190A0 (fi) 2007-03-05
FI120738B (fi) 2010-02-15

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