WO2016117024A1 - Bioréacteur pourvu d'un dispositif d'alimentation en micro/nanobulles contenant de l'oxygène et en micro/nanobulles contenant un gaz microbicide - Google Patents

Bioréacteur pourvu d'un dispositif d'alimentation en micro/nanobulles contenant de l'oxygène et en micro/nanobulles contenant un gaz microbicide Download PDF

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WO2016117024A1
WO2016117024A1 PCT/JP2015/051349 JP2015051349W WO2016117024A1 WO 2016117024 A1 WO2016117024 A1 WO 2016117024A1 JP 2015051349 W JP2015051349 W JP 2015051349W WO 2016117024 A1 WO2016117024 A1 WO 2016117024A1
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Prior art keywords
micro
biological reaction
nano
culture
washing
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PCT/JP2015/051349
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English (en)
Japanese (ja)
Inventor
信秀 国友
宏記 藤井
伸宏 田中
和矩 熊田
正守 樋口
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三菱化学エンジニアリング株式会社
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Priority to PCT/JP2015/051349 priority Critical patent/WO2016117024A1/fr
Priority to JP2016570680A priority patent/JP6850609B2/ja
Priority to PCT/JP2016/051567 priority patent/WO2016117599A1/fr
Publication of WO2016117024A1 publication Critical patent/WO2016117024A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D65/00—Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
    • B01D65/02—Membrane cleaning or sterilisation ; Membrane regeneration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D65/00—Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
    • B01D65/02—Membrane cleaning or sterilisation ; Membrane regeneration
    • B01D65/06—Membrane cleaning or sterilisation ; Membrane regeneration with special washing compositions
    • 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
    • C12M1/00—Apparatus for enzymology or microbiology
    • 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
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/04—Apparatus for enzymology or microbiology with gas introduction means
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor

Definitions

  • the present invention relates to a biological reaction apparatus for culturing microorganisms or cells (hereinafter referred to as “microorganisms”) and a biological reaction method using the biological reaction apparatus, and oxygen is contained in a culture solution containing microorganisms or the like at the time of biological reaction.
  • the entire inside of the biological culture apparatus including the filter is washed and sterilized.
  • a biological reaction is carried out in which microorganisms and the like are cultured in a culture tank to produce chemicals such as organic acids and alcohols and useful chemical substances such as antibodies.
  • Bio reactions differ from chemical reactions in that the reaction itself is slow, but because it does not use much energy and many chemical substances, it is a mild and meaningful reaction for the environment.
  • the biological reaction generally has a problem that the reaction is mild and slow. That is, for chemical reactions, a reaction within one hour is often sufficient, whereas in the case of biological reactions, a reaction time of several days or longer, several days or particularly several weeks or longer is required. There is also. For this reason, it is required to perform biological reactions efficiently and economically.
  • Patent Document 1 discloses that cell growth is promoted by culturing cells in a culture solution containing microbubbles.
  • Patent Documents 2 to 5 in the culture of microorganisms, the presence of micro-nano bubbles or nano bubbles in the culture solution promotes the activation of microorganisms, improves the reaction efficiency of biological reactions, shortens the reaction time, etc. Is disclosed.
  • Patent Document 1 describes that a microbubble is contained in the filtrate taken out of the culture solution in the culture vessel and supplied to the culture vessel.
  • Patent Document 2 describes that in a batch system, a culture solution is extracted from a culture tank, filtered through a bacterial cell filter to obtain a filtrate, and micronano bubbles are mixed with the filtrate and returned to the culture tank. ing.
  • Patent Document 3 describes mixing micro-nano bubbles and nano bubbles in the culture solution before supplying the culture solution to the culture vessel.
  • Patent Document 4 supplies the culture solution to the culture vessel. It is described that the micro / nano bubbles are mixed in the previous stage.
  • the conventional sterilization method requires sterilization equipment and labor, and particularly for sterilization of filtration membranes. 1) having a complicated shape; 2) When the filtration membrane is dried, the filtration function is reduced. 3) Since the filtration membrane is inferior in heat resistance as compared with the culture tank and peripheral equipment, it is difficult to sterilize the details sufficiently without deteriorating the function of the filtration membrane.
  • JP 2011-120535 A Japanese Patent No. 4146476 Japanese Patent No. 4805120 Japanese Patent No. 4956552 JP 61-242605 A Japanese Patent Publication No. 08-004726 JP 2013-226486 A
  • the subject of the biological reaction apparatus of this invention and the biological reaction method using this biological reaction apparatus is that the biological reaction using microorganisms etc. can be performed efficiently and economically at the time of biological reaction, and it is washed after completion of the biological reaction.
  • the object of the present invention is to provide a biological reaction device capable of economically and sufficiently performing cleaning and sterilization of a biological reaction device, particularly a filtration membrane, and a biological reaction method using this biological reaction device during sterilization.
  • the biological reaction device of the present invention and the biological reaction method using this biological reaction device are prepared by a micro / nano bubble generator provided in the biological reaction device, to a culture solution containing microorganisms or the like during a biological reaction, Micro-nano bubbles containing oxygen (hereinafter referred to as “micro-nano bubbles of oxygen”) are contained, and at the time of cleaning and sterilization, micro-nano bubbles (hereinafter referred to as “ozone”) containing a sterilizing gas such as ozone in the cleaning liquid. Etc.) ”).).
  • micro-nano bubbles of oxygen containing oxygen
  • ozone micro-nano bubbles containing a sterilizing gas such as ozone in the cleaning liquid. Etc.
  • micro nano bubble of the present invention means “micro bubble” and / or “nano bubble”. While “normal bubbles” rapidly rise in water and burst and disappear on the surface, microbubbles with a diameter of 50 ⁇ m or less called “microbubbles” shrink in water and disappear. Together with free radicals, “nanobubbles”, which are ultrafine bubbles having a diameter of 100 nm or less, are generated, and these “nanobubbles” remain in water for a certain amount of time.
  • Nano bubbles which are very small bubbles, are also called “ultra fine bubbles”.
  • ISO International Organization for Standardization
  • the creation of an international standard for fine bubble technology is being considered, and once the international standard is created, the name of “nanobubble”, which is currently commonly used, There is a possibility that it will be unified into “Ultra Fine Bubble”.
  • ozone As the “gas having bactericidal properties such as ozone” contained in the micro-nano bubbles such as ozone of the present invention, ozone, carbon dioxide (CO 2 ), chlorine dioxide (ClO 2 ), or a mixture thereof can be used. However, it is preferable to use ozone alone from the viewpoints of sterilization and handling.
  • the present invention generates micro / nano bubbles that remain in water for a long time using a micro / nano bubble generator, and in the culture reaction containing microorganisms or the like during a biological reaction, Can be used efficiently and economically, and at the time of cleaning and sterilization, the cleaning liquid contains micro-nano bubbles such as ozone to clean and sterilize biological reaction devices, especially filtration membranes. Economical and sufficient.
  • the biological reaction of the present invention is to cause a microorganism or the like to produce a reaction product using a culture solution as a nutrient source in a culture solution containing microorganisms or the like housed in a culture tank.
  • a culture solution containing a saccharide and a nitrogen source is used.
  • saccharides saccharides such as maltose, sucrose, glucose, fructose, and mixtures thereof are usually used.
  • concentration of saccharides in the culture solution is not particularly limited, but is set to 0.1 to 10 w / v%. preferable.
  • nitrogen source ammonium chloride, ammonium sulfate, corn steep liquor, yeast extract, meat extract, peptone or the like is used, and it is preferably set to 0.1 to 10 w / v%.
  • vitamins, inorganic salts, and the like is added to the culture solution as needed in addition to the saccharides and nitrogen source.
  • Examples of the cell in the present invention include an animal cell for producing a physiologically active peptide or protein used as an antibody drug, particularly a genetically modified animal cell.
  • microorganisms such as Aspergillus oryzae, natto, acetic acid, yeast, lactic acid, and other aerobic microorganisms that are conventionally used in technical fields such as brewing and fermentation, etc.
  • Various aerobic microorganisms can be used.
  • the reaction product produced in the culture tank is extracted from the culture tank together with a culture solution containing microorganisms and the like, separated into microorganisms and filtrate with a filter, and the reaction product is recovered from the filtrate.
  • the filter of the present invention comprises a filtration membrane and a container that accommodates the filtration membrane.
  • the filtration membrane may be an organic membrane or an inorganic membrane.
  • As the shape of the filtration membrane any shape such as a flat membrane, a hollow fiber membrane, and a spiral type can be adopted. Among these, a hollow fiber membrane module is preferable, and any one of an external pressure type and an internal pressure type can be adopted as long as it is a hollow fiber membrane module.
  • a culture solution containing reaction products, microorganisms and the like is filtered while being supplied to the inside of the hollow fiber membrane, and the filtrate is taken out from the outside through the hollow fiber membrane. Since membrane dirt such as accumulated microorganisms is scraped off by the shearing force generated by the parallel flow of the culture solution, a stable filtration state can be maintained over a long period of time.
  • steady operation is performed at a circulation flow rate of about 1 to 2 m / s when using an organic membrane and about 1 to 3 m / s when using a ceramic membrane.
  • a circulation flow rate of about 1 to 2 m / s when using an organic membrane and about 1 to 3 m / s when using a ceramic membrane.
  • the circulation rate can be reduced to about 0.2 to 1.5 m / s.
  • the flux can be increased by about 1.2 to 2.0 times.
  • an organic polymer compound can be suitably used from the viewpoints of separation performance, water permeability, and dirt resistance.
  • examples include polyethylene resins, polypropylene resins, polyvinyl chloride resins, polyvinylidene fluoride resins, polysulfone resins, polyethersulfone resins, polyacrylonitrile resins, cellulose resins, and cellulose triacetate resins. A mixture of these resins as the main component may be used.
  • a vinylidene chloride resin or a resin containing the vinylidene fluoride resin as a main component is more preferably used because it has a characteristic of having both chemical strength (particularly chemical resistance) and physical strength.
  • the polyvinylidene fluoride-based resin a homopolymer of vinylidene fluoride is preferably used.
  • the polyvinylidene fluoride resin may be a copolymer of a vinyl monomer copolymerizable with vinylidene fluoride.
  • vinyl monomers copolymerizable with vinylidene fluoride include tetrafluoroethylene, hexafluoropropylene, and ethylene trichloride fluoride.
  • the average pore diameter of the filtration membrane can be appropriately determined according to the purpose and situation of use, but it is preferably smaller to some extent, and is usually preferably 0.01 ⁇ m or more and 1 ⁇ m or less.
  • the average pore diameter of the hollow fiber membrane is less than 0.01 ⁇ m, components such as microorganisms, such as sugars and proteins, and membrane dirt components such as aggregates thereof block the pores, and stable operation cannot be performed.
  • it is preferably 0.02 ⁇ m or more, and more preferably 0.03 ⁇ m or more.
  • the average pore diameter approaches the size of a microorganism or the like, these may directly block the pores.
  • the average pore diameter is 0.4 ⁇ m. The following is preferable, and 0.2 ⁇ m or less is preferable.
  • the average pore diameter of the filtration membrane can be obtained by measuring and averaging the diameters of a plurality of pores observed by scanning electron microscope observation at a magnification of 10,000 times or more.
  • 10 or more, preferably 20 or more pores are randomly selected, the diameters of these pores are measured, and the number average is obtained.
  • an image processing device or the like it is also preferable to use an image processing device or the like to obtain a circle having an area equal to the area of the pores, that is, an equivalent circle, and obtain the equivalent circle diameter as the pore diameter. it can.
  • the recovery of the target product may be performed batchwise or continuously.
  • the culture tank pump is driven to transfer the filtered filtrate to the filtrate storage tank.
  • the filtered filtrate is balanced with the amount of the culture solution supplied to the culture vessel so that the water level of the culture solution containing microorganisms in the culture vessel is kept constant. Extract and transfer to the filtrate storage tank.
  • the batch type or the continuous type can be selected as appropriate in consideration of the efficiency of biological reaction, the required purity of the target product, economy, and the like.
  • micronanobubbles of oxygen are generated by a micronanobubble generator, and the micronanobubbles are contained in a culture solution containing microorganisms, and 2) At the time of washing and sterilization, the micronanobubble generator is used. Micronano bubbles such as ozone are generated, and the micronano bubbles are contained in the cleaning liquid.
  • a means for containing micro-nano bubbles in a culture solution or washing solution containing microorganisms a) means for releasing the micro / nano bubbles into the culture solution containing microorganisms in the culture tank by the micro / nano bubble generator provided outside the culture tank; b) Means for containing micro / nano bubbles in the culture solution supplied to the culture tank by the micro / nano bubble generator provided in the conduit for supplying the culture solution to the culture tank, c) Means for causing the filtrate collected from the culture solution containing microorganisms or the like to contain micro / nano bubbles by a micro / nano bubble generator, and refluxing the filtrate containing the micro / nano bubbles to the culture tank, d)
  • a means for supplying a culture solution containing micro-nano bubbles in advance to a culture tank through a pipe line can be employed.
  • the means with the least stress and damage to microorganisms is the means b) and d) above.
  • stress and damage are given to microorganisms and the like by the shearing force generated by the release of micro-nano bubbles in the means a) and the shearing force generated during filtration in the means c).
  • the micro / nano bubble generating device As the micro / nano bubble generating device, a known or commercially available device can be used. Specifically, for example, after a sufficient amount of gas is dissolved in water at a certain high pressure, the pressure is released to create a supersaturated condition of the dissolved gas, a “pressure dissolution type microbubble generator”, “Gas-liquid two-phase flow swirl type microbubble generator” that uses the phenomenon of generating a vortex by generating a water flow, entraining large bubbles in the vortex, and breaking the vortex into bubbles. Can be used.
  • micro / nano bubble generating apparatus examples include, for example, JP 2007-31690 A, JP 2006-289183 A, JP 2005-245817 A, JP 2007-136255 A, and JP 2009-39600 A. Can be used.
  • this micro-nano bubble generator is used to make oxygen containing micro-nano bubbles contained in a culture solution containing microorganisms at the time of biological reaction, and in the washing solution at the time of cleaning / sterilization.
  • the generation of oxygen micro-nano bubbles and the generation of micro-nano bubbles such as ozone may be performed with the same micro-nano bubble generation device, or separate micro-nano bubble generation devices are used. You may go.
  • the same micro / nano bubble generator is used, the supply of the gas containing oxygen and the supply of the gas containing ozone or the like to this device are switched by a switching valve or the like.
  • oxygen containing micro-nano bubbles is contained in a culture solution containing microorganisms or the like during a biological reaction. From the viewpoint of efficiently supplying oxygen necessary for respiration to microorganisms or the like, the oxygen content of the micro-nano bubbles is determined. It is preferable to set it high.
  • cleaning and sterilization can be economically and sufficiently performed to the details of the biological reaction device, particularly the filtration membrane, by including micro-nano bubbles such as ozone in the cleaning liquid during cleaning and sterilization.
  • ozone can be suitably used as the “bactericidal gas such as ozone” contained in micro-nano bubbles such as ozone, but ozone is generally irradiated with a short wavelength ultraviolet ray by a mercury lamp, It can be generated from air or oxygen by low-temperature discharge or the like with high voltage.
  • the amount of ozone supplied to the cleaning liquid varies depending on the type of bacteria to be sterilized, temperature, pH, etc., but it is preferable to supply the ozone concentration in the cleaning liquid to be around 1 ppm. If the ozone concentration in the cleaning liquid is too low, the sterilizing power is insufficient, and in particular, the details of the filtration membrane cannot be sufficiently sterilized. On the other hand, when the ozone concentration in the cleaning liquid is too high, it is not economical, and the inside of the biological reaction apparatus, the filtration membrane, and the like may be deteriorated.
  • the cleaning liquid containing micro-nano bubbles such as ozone
  • water such as ion exchange water, reverse osmosis membrane permeated water, distilled water, and alcohols
  • alcohols include monohydric alcohols such as 1-butanol, 2-butanol and 1-heptanol, ethylene glycol, 1,2-propanediol, 1,3-propanediol, diethylene glycol, triethylene glycol, glycerin and the like.
  • butyl cellosolve, phenyl cellosolve and the like are exemplified. Silicone oil or water to which a surfactant is added can also be used.
  • the cleaning solution may be one in which an electrolyte is dissolved in water, or one in which an alkali, an acid, an oxidizing agent, or a reducing agent is added.
  • an additive those that do not adversely affect the filtration membrane, the module member, etc. due to the generation of decomposition products are preferably used.
  • water containing no additive is preferable in that even if it is mixed in the filtrate, the change given to the properties of the filtrate is small.
  • a hydrophobic filtration membrane is used, for example, by immersing the hydrophobic filtration membrane in water-compatible glycerin, or once replacing glycerin with alcohol, glycerin Since water can be replaced with water, water can be selected as the liquid of the hydrophobic filtration membrane.
  • Cleaning and sterilization is usually performed in the following steps. 1) Remove the microorganism used for the biological reaction and the culture solution containing the microorganism from the biological reaction apparatus. 2) A washing liquid is accommodated in the culture tank, and micro-nano bubbles such as ozone are contained in the washing liquid. In addition, the inclusion of micro-nano bubbles such as ozone in the washing liquid is performed as described in a) to d) above.
  • the washing liquid stored in the culture tank, the washing liquid supplied to the culture tank, and the filtration membrane are passed through the filtration tank. This is performed on the washing solution to be refluxed and / or the washing solution before being supplied to the culture tank.
  • the cleaning liquid containing micro-nano bubbles such as ozone is flowed in the same route as the flow of the culture liquid or the filtrate containing microorganisms or the like to clean and sterilize the inside of the biological reaction apparatus.
  • the inside of the biological reaction device can be cleaned and sterilized using the device for carrying out the biological reaction as it is.
  • corners inside the biological reaction apparatus, pores of the filtration membrane, etc. which are difficult to clean and sterilize by ordinary methods, can be sufficiently cleaned and sterilized.
  • the filtration membrane has a large number of pores, and it is difficult to sufficiently sterilize organic substances such as microorganisms clogged in these pores.
  • the cleaning liquid is supplied to the primary side of the filter of the above 1) to 3), and the filtration membrane is cleaned and sterilized by filtering to the secondary side of the filter (hereinafter referred to as “order washing”).
  • order washing filtering to the secondary side of the filter
  • a cleaning liquid containing micro-nano bubbles such as ozone is supplied from a pipe connected to the secondary side of the filter, and the filtration membrane is washed and sterilized by filtering the primary side of the filter. Is to do.
  • the washing liquid after washing and sterilizing the filtration membrane may be discharged to the outside of the biological reaction apparatus, or may be refluxed to the culture tank to wash and sterilize the culture tank. Since the cleaning liquid that has washed and sterilized the filtration membrane in the initial stage of washing contains microorganisms and other organic substances at a high concentration, the cleaning liquid is discharged out of the biological reaction apparatus in the initial stage of washing, and the filtration membrane is sufficiently large. It is preferable that the washing liquid is refluxed to the culture tank and the inside of the culture tank is washed and sterilized at the stage of being washed and sterilized.
  • the washing liquid after washing and sterilizing the filtration membrane may be discharged from the outlet of the filter by one washing and sterilization, or returned to the inlet of the filter and washed and sterilized again.
  • the cleaning liquid that has washed and sterilized the membrane at the initial stage of washing contains microorganisms and other organic substances at a high concentration, so it is discharged from the outlet of the filter. Is preferably returned to the inlet of the filter to clean and sterilize the filter membrane again, since the cleaning solution can be saved.
  • washing and sterilizing the inside of the culture tank with the washing solution it is preferable to spray the washing solution over a wide range like a shower because the inner wall of the cultivation tank can be sufficiently washed and sterilized.
  • Washing and sterilization is performed in a time that can be sufficiently washed and sterilized according to the condition of the filtration membrane and the resistance of microorganisms.
  • the biological reaction apparatus of the present invention and the biological reaction method using this biological reaction apparatus can efficiently and economically perform a biological reaction using microorganisms or the like during a biological reaction.
  • the biological reaction apparatus in particular, the filtration membrane and the like can be cleaned and sterilized economically and sufficiently.
  • the biological reaction is carried out with a culture solution containing microorganisms containing oxygen micro-nano bubbles, a porous structure having a high loading density in which microorganisms are supported to the back of the pores. Even when it is used, oxygen necessary for respiration can be sufficiently supplied to microorganisms or the like carried in the back of the pores of the porous structure, so that the efficiency of biological reaction can be improved. In this case, filtration can be performed efficiently and economically, and stress and damage given to microorganisms can be reduced.
  • the biological reaction apparatus of the present invention and the biological reaction method using this biological reaction apparatus can efficiently and economically perform biological reactions using microorganisms using micro-nano bubbles.
  • the present invention is useful not only for the production of foods, chemicals, chemicals and the like using biological reactions such as fermentation, but also for biorefinery for producing bioethanol and the like using biomass.
  • FIG. 1 schematically shows a first embodiment of the biological reaction apparatus of the present invention.
  • the culture tank 1 is provided with a culture tank agitator 17 for stirring the culture solution 6 containing microorganisms and the like.
  • the culture solution 7 supplied to the culture tank 1 to contain micronanobubbles of oxygen by the micro / nano bubble generating device 3 provided in the conduit for supplying the culture solution 7 to the culture tank 1; and b) culturing.
  • the micro / nano bubble generator 2 provided outside the tank 1, the culture liquid 6 containing microorganisms or the like in the culture tank 1 is caused to contain oxygen micro / nano bubbles.
  • the reaction product generated in the culture tank 1 was extracted from the culture tank 1 together with the culture solution 6 containing microorganisms or the like by the culture tank pump 11, and the filtrate and the filtrate were removed in the filter 10.
  • the filtrate is stored in the filtrate storage tank 16 with the valve 12 and the valve 13 opened, separated into a culture solution 6 (hereinafter referred to as “concentrated solution of microorganisms”) containing microorganisms, etc.
  • the concentrated solution is refluxed to the culture tank 1 through a pipe line.
  • the micro-nano bubble generator 3 contains micro-nano bubbles such as ozone in the cleaning liquid supplied to the culture tank 1 instead of the culture liquid 7; and b) the micro-nano bubble generator 2 contains the micro-nano bubble generator 2 in the culture tank 1.
  • the cleaning liquid is made to contain micro-nano bubbles such as ozone.
  • the inside of the culture tank 1 is cleaned and sterilized with a cleaning liquid that sufficiently contains micro-nano bubbles such as ozone.
  • a washing liquid sufficiently containing micro-nano bubbles such as ozone is extracted from the culture tank 1 by the culture tank pump 11, the valve 12 is closed, the valve 13 is opened, and the filtration membrane of the filter 10 is washed and sterilized (in order).
  • the inside of the pipe line of the filter 10 ⁇ the filtrate storage tank 16 is washed and sterilized. If the valve 12 is opened and the valve 13 is closed, the inside of the pipe line of the filter 10 ⁇ the culture tank 1 can be washed and sterilized.
  • the cleaning solution containing micro-nano bubbles such as ozone is distributed to the details of the filter membrane of the filter in the same way as the culture solution and the filtrate. Therefore, it must be thoroughly cleaned and sterilized without placing a burden on the filter membrane. Can do.
  • the concentrates such as microorganisms isolate
  • concentration of microorganisms etc. in the culture tank 1 can be maintained high. .
  • FIG. 2 schematically shows a second embodiment of the biological reaction apparatus of the present invention.
  • the micro / nano bubble generator 4 instead of the micro / nano bubble generators 2 and 3 in the first embodiment, the micro / nano bubble generator 4 is used, and the micronano bubbles are contained in the filtrate of microorganisms or the like and returned to the culture tank 1. It is what you do.
  • the function of selecting whether to discharge from the outlet of the filter or to return to the inlet of the filter when washing and sterilizing Is provided.
  • the functions of 1) and 2) can be provided as appropriate in other embodiments.
  • oxygen micro-nano bubbles are contained in a culture solution containing microorganisms or the like during a biological reaction, and ozone or the like is contained in the washing solution during cleaning or sterilization as follows. Inclusion of nanobubbles is performed.
  • the culture solution 6 containing the microorganisms and the filtrate are removed from the culture tank 1 and the filtrate storage tank 16, respectively.
  • A) The culture tank 1 is replaced with the culture solution 7. Supply cleaning solution.
  • b) The valve 13, valve 14, valve 21, valve 23 and valve 24 are closed, the valve 12 and valve 22 are opened, the culture tank pump 11 is driven, and the filter membrane of the filter 10 is mainly washed.
  • a cleaning liquid containing a high concentration of microorganisms and other organic substances is discharged out of the biological reaction apparatus.
  • the valve 13, valve 14, valve 22, valve 23, and valve 24 are closed, and the culture tank pump 11 is opened by opening the valve 12 and valve 21.
  • the cleaning liquid is guided to the micro / nano bubble generating device 4 through the culture tank 1 ⁇ filter 10 ⁇ valve 12, and the cleaning liquid containing micro / nano bubbles such as ozone is returned to the culture tank 1, thereby forming the cleaning liquid.
  • the inside of the culture tank 1, the filter membrane of the filter 10, the culture tank 1 ⁇ the filter 10 ⁇ the valve 12 ⁇ the micro-nano bubble generator 4 ⁇ the inside of the pipe line of the culture tank 1, etc.
  • the washing liquid sufficiently containing micro-nano bubbles such as ozone is extracted from the culture tank 1 by the culture tank pump 11, the valve 12 and the valve 14 are closed, and the valve 13 is opened.
  • the membrane can be cleaned and sterilized (in order), and the inside of the pipe line of the filter 10 ⁇ the valve 13 ⁇ the filtrate storage tank 16 can be cleaned and sterilized. If the valve 12 and the valve 13 are closed and the valve 14 is opened, the inside of the pipe line of the filter 10 ⁇ the valve 14 ⁇ the culture tank 1 can be washed and sterilized.
  • washing and sterilization can be performed by the same operation as the biological reaction, and sufficient washing and sterilization can be performed without placing a burden on the filtration membrane. it can.
  • the filter 10 Since the micro-nano bubbles are included in the filtrate separated by the filter 10, stress and damage given to microorganisms can be reduced, and the filter 10 Since the concentrated liquid such as microorganisms separated in step 1 is returned to the culture tank 1, the concentration of microorganisms and the like in the culture tank 1 can be maintained high.
  • FIG. 3 schematically shows a third embodiment of the biological reaction apparatus of the present invention.
  • a means for adding micro / nano bubbles to the culture solution 6 containing microorganisms and the like in the culture tank 1 used in the first embodiment is used in the second embodiment.
  • the culture solution 7 supplied to the culture tank 1 is used in combination with means for containing micro / nano bubbles (micro / nano bubble generator 3).
  • FIG. 4 schematically shows a fourth embodiment of the biological reaction apparatus of the present invention.
  • the fourth embodiment is characterized in that a supporting structure 8 in which a microorganism or the like is supported on a porous structure such as a polyvinyl alcohol porous gel is used.
  • oxygen micro-nano bubbles are contained in the culture solution during biological reaction, and micro-nano bubbles such as ozone are contained in the washing solution during cleaning and sterilization as follows. Is called.
  • the culture solution 7 is supplied to the culture tank 1. b) Opening the valve 12 and closing the valve 13 to drive the culture tank pump 11, leading the filtrate separated by the filter 10 provided in the culture tank 1 to the micro / nano bubble generating device 4, and containing oxygen micro / nano bubbles Then, return to the culture tank 1. c) The reaction product produced in the culture tank 1 is recovered together with the filtrate by opening the valve 13 at an appropriate time, and stored in the filtrate storage tank 16.
  • the culture solution 6 containing the microorganisms and the filtrate are removed from the culture tank 1 and the filtrate storage tank 16, respectively.
  • the inside of the pipe line of the tank 1 is cleaned and sterilized, and the filter membrane of the filter 10 is cleaned and sterilized (in order).
  • the washing liquid sufficiently containing micro-nano bubbles such as ozone is extracted from the culture tank 1 through the filter 10 by the culture tank pump 11, and the valve 12 and the valve 14 are closed and the valve 13 is opened.
  • the filter membrane of the filter 10 can be washed and sterilized again (in order), and the inside of the pipe line of the filter 10 ⁇ the valve 13 ⁇ the filtrate storage tank 16 can be cleaned and sterilized.
  • the fourth embodiment has the following features by using the supporting structure 8 that supports microorganisms or the like.
  • the density of microorganisms or the like in the culture tank 1 can be increased, the efficiency of biological reaction can be increased.
  • O It is not necessary to employ a microfilter usually used in the technical field of brewing or fermentation as a filter 10 for separating microorganisms from a culture solution 6 containing microorganisms, and an organic polymer such as polyvinylidene fluoride. Since a flat membrane with low filtration accuracy such as a porous membrane made of a compound or a metal wire mesh can be adopted, the filtration step can be carried out economically and efficiently. ⁇ Biological reactions can be performed efficiently and economically without causing significant stress or damage to microorganisms.
  • FIG. 5 schematically shows a fifth embodiment of the biological reaction apparatus of the present invention.
  • the supporting structure 8 supporting microorganisms or the like in the fourth embodiment is fixed in the culture tank 1 by a fixing member 9 such as a column or a net.
  • the inclusion of micronanobubbles of oxygen in the culture solution 6 containing microorganisms and the like in the biological reaction and the inclusion of micronanobubbles such as ozone in the cleaning solution at the time of cleaning and sterilization This is performed in the same manner as in the fourth embodiment.
  • the support structure 8 supporting microorganisms or the like is fixed in the culture tank 1, the support structure 8 is less likely to be damaged or destroyed. Features such as little desorption.
  • FIG. 6 schematically shows a sixth embodiment of the biological reaction apparatus of the present invention.
  • a cleaning liquid containing micro-nano bubbles such as ozone
  • the following operation 1) at the time of a biological reaction similar to the second embodiment and the operation 2 of the forward washing at the time of washing and sterilization are as follows. ) Is performed. 1) At the time of biological reaction a) The culture solution 7 is supplied to the culture tank 1. b) The valve 13 is closed, the valve 12 and the valve 14 are opened, the culture tank pump 11 is driven, and the concentrated liquid such as microorganisms separated by the filter 10 is returned to the culture tank 1 through the conduit, and the filter 10 The filtrate separated in (1) is guided to the micro / nano bubble generator 4 to contain oxygen micro / nano bubbles and then returned to the culture tank 1.
  • the washing liquid containing micro-nano bubbles such as ozone By returning the washing liquid containing micro-nano bubbles such as ozone to the culture tank 1, the inside of the culture tank 1 and the culture tank 1 ⁇ the filter 10 ⁇ the valve 12 ⁇ the micro / nano bubble generator while containing the micro-nano bubbles such as ozone in the washing liquid. 4 ⁇ Wash and sterilize the inside of the pipe of the culture tank 1. c) After that, the washing liquid sufficiently containing micro-nano bubbles such as ozone is extracted from the culture tank 1 by the culture tank pump 11, the valve 12 and the valve 14 are closed, and the valve 13 is opened. The membrane can be cleaned and sterilized (in order), and the inside of the pipe line of the filter 10 ⁇ the valve 13 ⁇ the filtrate storage tank 16 can be cleaned and sterilized. If the valve 12 and the valve 13 are closed and the valve 14 is opened, the inside of the pipe line of the filter 10 ⁇ the valve 14 ⁇ the culture tank 1 can be washed and steriliz
  • the washing and sterilization can be performed by the same operation as the biological reaction, and the washing and sterilization can be sufficiently performed without imposing a burden on the filtration membrane. It is possible to reduce the stress and damage given to the etc., and to maintain a high concentration of microorganisms in the culture tank.
  • the backwashing of the filtration membrane of the following 3) is performed together with the sequential washing of the above 2).
  • the filtration membrane is back-washed by the following steps d) to f).
  • the pump (not shown) is driven to guide the cleaning liquid in the cleaning liquid tank 19 to the micro / nano bubble generating device 5. Then, micro-nano bubbles such as ozone are included in the cleaning liquid.
  • a cleaning liquid containing micro-nano bubbles such as ozone is supplied to the secondary side of the filter 10, filtered to the primary side of the filter 10, and the filter membrane is back-washed for cleaning and sterilization. . f) The washing water after backwashing the filtration membrane is discharged to the outside through the valve 20.
  • the forward washing in 2) and the back washing in 3) are repeated a plurality of times as necessary.
  • the filtration membrane is washed and sterilized because it has a large number of pores, and the washing and sterilization of the filtration membrane, which requires time and effort for washing and sterilization, is performed using both forward washing and backwashing. It has the features that it can be performed sufficiently and the cleaning and sterilization time can be shortened.

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Abstract

Le problème abordé par la présente invention est de pourvoir à un bioréacteur capable d'effectuer des réactions biologiques qui utilisent des microorganismes ou des cellules de manière efficace et économique, le bioréacteur, et, en particulier, un film de filtration, etc. de celui-ci pouvant être minutieusement et économiquement nettoyé et stérilisé. Un procédé de type réaction biologique utilisant le bioréacteur est en outre décrit. La solution selon l'invention porte sur un bioréacteur et un procédé de type réaction biologique l'utilisant qui sont caractérisés en ce que des micro/nano-bulles qui contiennent de l'oxygène sont incorporées dans une solution de culture (7) et en ce que des micro/nano-bulles qui contiennent un gaz microbicide tel que l'ozone sont incorporées dans un liquide de nettoyage.
PCT/JP2015/051349 2015-01-20 2015-01-20 Bioréacteur pourvu d'un dispositif d'alimentation en micro/nanobulles contenant de l'oxygène et en micro/nanobulles contenant un gaz microbicide WO2016117024A1 (fr)

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PCT/JP2015/051349 WO2016117024A1 (fr) 2015-01-20 2015-01-20 Bioréacteur pourvu d'un dispositif d'alimentation en micro/nanobulles contenant de l'oxygène et en micro/nanobulles contenant un gaz microbicide
JP2016570680A JP6850609B2 (ja) 2015-01-20 2016-01-20 酸素を含有するマイクロナノバブル及びオゾン等の殺菌性を有する気体を含有するマイクロナノバブルを供給する装置を備えた生物反応装置
PCT/JP2016/051567 WO2016117599A1 (fr) 2015-01-20 2016-01-20 Bioréacteur doté d'un dispositif pour fournir des micro/nano-bulles contenant de l'oxygène et des micro/nano-bulles contenant un gaz microbicide tel que l'ozone

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PCT/JP2015/051349 WO2016117024A1 (fr) 2015-01-20 2015-01-20 Bioréacteur pourvu d'un dispositif d'alimentation en micro/nanobulles contenant de l'oxygène et en micro/nanobulles contenant un gaz microbicide

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PCT/JP2016/051567 WO2016117599A1 (fr) 2015-01-20 2016-01-20 Bioréacteur doté d'un dispositif pour fournir des micro/nano-bulles contenant de l'oxygène et des micro/nano-bulles contenant un gaz microbicide tel que l'ozone

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WO2020209036A1 (fr) * 2019-04-10 2020-10-15 野村マイクロ・サイエンス株式会社 Procédé pour nettoyer des dispositifs de dégazage à membrane et système pour produire de l'eau ultra pure
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CN114918236A (zh) * 2022-05-11 2022-08-19 山东大学 一种垃圾焚烧飞灰水洗反应装置、处理系统及方法
CN114918236B (zh) * 2022-05-11 2023-12-19 山东大学 一种垃圾焚烧飞灰水洗反应装置、处理系统及方法

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