WO2017141394A1 - Dispositif de réaction pour effectuer une centrifugation - Google Patents

Dispositif de réaction pour effectuer une centrifugation Download PDF

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Publication number
WO2017141394A1
WO2017141394A1 PCT/JP2016/054671 JP2016054671W WO2017141394A1 WO 2017141394 A1 WO2017141394 A1 WO 2017141394A1 JP 2016054671 W JP2016054671 W JP 2016054671W WO 2017141394 A1 WO2017141394 A1 WO 2017141394A1
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WO
WIPO (PCT)
Prior art keywords
reaction
reaction vessel
housing
permanent magnet
liquid
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PCT/JP2016/054671
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English (en)
Japanese (ja)
Inventor
石川　陽一
Original Assignee
エイブル株式会社
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Application filed by エイブル株式会社 filed Critical エイブル株式会社
Priority to PCT/JP2016/054671 priority Critical patent/WO2017141394A1/fr
Priority to JP2017506945A priority patent/JPWO2017141394A1/ja
Publication of WO2017141394A1 publication Critical patent/WO2017141394A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/28—Moving reactors, e.g. rotary drums
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B1/00—Centrifuges with rotary bowls provided with solid jackets for separating predominantly liquid mixtures with or without solid particles
    • B04B1/02—Centrifuges with rotary bowls provided with solid jackets for separating predominantly liquid mixtures with or without solid particles without inserted separating walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B5/00—Other centrifuges
    • B04B5/12—Centrifuges in which rotors other than bowls generate centrifugal effects in stationary containers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B9/00—Drives specially designed for centrifuges; Arrangement or disposition of transmission gearing; Suspending or balancing rotary bowls
    • B04B9/08—Arrangement or disposition of transmission gearing ; Couplings; Brakes
    • 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
    • C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus

Definitions

  • the present invention relates to a reaction apparatus.
  • the present invention relates to a reaction apparatus capable of performing a centrifugal separation process.
  • a chemical, biochemical or biological reaction can be performed in a reaction vessel, and then the reaction vessel can be used as a rotor, and the reaction solution can be centrifuged to perform solid-liquid separation.
  • the present invention can be used effectively not only for chemical reactions but also for biochemical reactions such as microorganisms, animal and plant cell culture, cell concentration, and perfusion culture.
  • examples of chemical reactions include narrowly defined chemical reactions and biochemical reactions.
  • the reaction solution containing crystals and the like is transferred from the reaction vessel (reaction vessel) to the centrifuge, and after solid-liquid separation, it is washed in the centrifuge if necessary. It is common practice to recover crystals.
  • a culture solution (reaction solution) obtained by culturing microorganisms or animal and plant cells is transferred from a culture vessel (reaction vessel) to a centrifuge, and after solid-liquid separation, solid content is obtained.
  • cell concentration and perfusion culture are widely performed by collecting the liquid.
  • centrifuges such as a bottle centrifuge and a shear press type centrifuge in which the reaction solution is transferred to a bottle or tube and then rotated.
  • a non-porous wall centrifuge rotates a cylindrical container and deposits a solid component having a large specific gravity in the liquid to be processed (reaction liquid) on the inner wall of the cylinder, and continuously supplies the liquid to be processed.
  • a method of continuous centrifugation is generally used.
  • Patent Document 1 a culture apparatus that also serves as a centrifuge is disclosed in, for example, Japanese Patent Laid-Open No. 5-76344 (Patent Document 1).
  • the culture tank rotary cylinder
  • This is a perfusion culture apparatus that pulls out of the tank by a pump with a supernatant extraction tube, then radiates liquid medium from above the inner wall toward cells deposited on the inner wall, disperses the cells in the liquid medium, and performs perfusion culture .
  • the stirring blade it is necessary to fold the stirring blade so that the stirring blade does not come into contact with the culture solution at the time of centrifugation, so that the structure of the culture tank becomes complicated and the supernatant extraction pipe
  • the structure of the apparatus becomes complicated.
  • the reaction vessel such as a culture tank is more difficult to clean as the internal structure becomes more complicated, and the conventional device has a problem that the structure of the device is complicated and the risk of contamination by microorganisms increases. is there.
  • the conventional apparatus is not necessarily suitable for so-called perfusion culture, in which only the supernatant is discharged while leaving cells, and a fresh liquid medium is supplied to the medium to exchange the medium.
  • an object of the present invention is to provide a reaction apparatus that also serves as a centrifugal separator, which can effectively perform solid-liquid separation by centrifugation and has a simple internal structure of the reaction vessel. is there.
  • the reaction vessel was rotated by the drive unit, and the solid-liquid separation of the reaction solution and the supernatant solution from the reaction vessel were performed by the centrifugal force.
  • the present invention includes the following aspects.
  • a bottomed cylindrical reaction vessel whose upper part is open at the peripheral edge, a substantially cylindrical housing that accommodates the reaction vessel inside, and the reaction vessel disposed outside the housing as an axis
  • a reaction device that also serves as a centrifuge and comprises a drive unit that is driven to rotate about an axis via a direction axis, and after the reaction of the content liquid used for the reaction in the reaction vessel, the reaction vessel
  • the reaction apparatus is configured to perform solid-liquid separation of the reaction liquid and overflow of the supernatant liquid from the upper opening end of the reaction container by centrifugal force by rotating the shaft around the axis.
  • the housing has a supply pipe for supplying the content liquid to the reaction container at an upper part thereof, and a discharge pipe for discharging the supernatant liquid overflowing from the peripheral part to the lower part of the side surface to the outside of the housing.
  • the reaction container includes a rim portion in an inner direction at a peripheral edge portion of an upper opening end.
  • the driving unit is driven by magnetic force.
  • the reaction vessel is rotatably attached to a support shaft that rises from a substantially central portion of a bottom portion in the housing.
  • the reaction container is a permanent magnet disposed horizontally at the bottom of the reaction container, and the permanent magnet disposed horizontally near the bottom of the housing at a position facing the permanent magnet.
  • the reaction apparatus according to (5) which is rotationally driven by a driving permanent magnet having a different polarity and the driving unit connected to the driving permanent magnet via a driving rotating shaft.
  • One end of the rotating shaft is connected to the center of the bottom of the outer side of the reaction vessel, and the other end of the rotating shaft is rotatably connected to the driving unit via a bearing on the bottom of the housing.
  • the reaction apparatus according to any one of 1) to (3).
  • the reaction apparatus according to any one of 4).
  • the reaction vessel has a permanent magnet arranged horizontally with respect to the rotation axis, and a different polarity from the permanent magnet arranged horizontally near the bottom of the housing at a position facing the permanent magnet.
  • the reaction apparatus according to (8) which is rotationally driven by a driving permanent magnet and the driving unit connected to the driving permanent magnet via a driving rotating shaft.
  • the reaction apparatus according to any one of (1) to (3), which is freely connected.
  • the reaction apparatus includes an agitation apparatus, and the agitation apparatus is suspended in a wing drive unit disposed on a lid on the upper part of the housing, and the reaction vessel that is connected to and rotated.
  • the reaction apparatus according to any one of (1) to (9), comprising: a rotating shaft for stirring; and a stirring blade attached in the vicinity of the lower part.
  • the reaction device includes a stirring device, and the stirring device is attached to a rotating shaft for stirring suspended inside the reaction vessel via a bearing of a lid on the upper part of the housing, and the vicinity of the lower part.
  • a stirring blade, and the stirring blade is disposed horizontally on the rotor near the bottom outside the housing at a position facing the permanent magnet for the blade, which is disposed horizontally on the stirring blade.
  • the wing permanent magnet and the wing drive permanent magnet having a different polarity, and the wing drive section for rotating the rotator via a rotation transmitting means, are rotated and driven by the reaction vessel.
  • the reaction apparatus according to (7), wherein the reaction apparatus is rotatably attached to a drive rotating shaft connected to a bottom part on the outside of the drive part and the drive part.
  • the liquid flow baffle member is a member that hangs from the lid on the upper part of the housing so that a part of the liquid flow baffle member is submerged in the content liquid inside the reaction vessel, and the reaction vessel is axially driven by the drive unit.
  • the reaction apparatus according to any one of (1) to (10), wherein the content liquid is agitated by rotating around.
  • the housing includes at least one of various sensors, a baffle plate, a liquid supply pipe, a gas supply pipe, an exhaust pipe, and a heat exchange pipe.
  • the reaction device according to any one of (1) to (14), further comprising a heater and / or a cooler outside the housing.
  • a reaction apparatus that can effectively perform solid-liquid separation by centrifugation and also has a simple internal structure of a reaction vessel.
  • the reaction vessel (culture tank) containing the reaction solution (culture solution) is rotated in the reaction device also used as a centrifuge of the present invention. Since it is driven to perform solid-liquid separation of the reaction liquid and overflow and discharge of the supernatant liquid from the top of the reaction vessel by centrifugal force, the above disadvantages are eliminated, and the solid supernatant liquid The solid-liquid separation can be effectively performed while preventing the mixture.
  • FIG. 1A is a schematic view showing one embodiment of the reaction apparatus of the present invention.
  • FIG. 1A is a schematic view showing an aspect in which a rim portion is not provided at the peripheral edge portion of the opening end of the upper part of the reaction vessel.
  • FIG. 1B is a schematic view showing one embodiment of the reaction apparatus of the present invention.
  • FIG. 1B is a schematic view showing an aspect having a rim portion in the inner direction at the peripheral edge portion of the open end of the upper portion of the reaction vessel.
  • FIG. 2A is a schematic view showing an embodiment of the reaction apparatus of the present invention, in which a portion for driving the reaction vessel is illustrated.
  • FIG. 2B is a schematic view showing an embodiment of the reaction apparatus of the present invention, in which a portion for driving the reaction vessel is illustrated.
  • FIG. 1A is a schematic view showing an aspect in which a rim portion is not provided at the peripheral edge portion of the opening end of the upper part of the reaction vessel.
  • FIG. 1B is a schematic view showing
  • FIG. 2C is a schematic view showing an embodiment of the reaction apparatus of the present invention, in which a portion for driving the reaction vessel is illustrated.
  • FIG. 2D is a schematic view showing an embodiment of the reaction apparatus of the present invention, in which a portion for driving the reaction vessel is illustrated.
  • FIG. 3A is a schematic view showing an embodiment of the reaction apparatus of the present invention, in which an embodiment of stirring the content liquid is illustrated.
  • FIG. 3B is a schematic view showing an embodiment of the reaction apparatus of the present invention, in which an embodiment of stirring the content liquid is illustrated.
  • FIG. 3C is a schematic view showing an embodiment of the reaction apparatus of the present invention, in which an embodiment of stirring the content liquid is illustrated.
  • FIG. 4A is a top view showing an embodiment of the reaction apparatus of the present invention.
  • FIG. 4B is a longitudinal sectional view showing an embodiment of the reaction apparatus of the present invention.
  • the present invention relates to a reaction apparatus capable of performing a centrifugal separation process.
  • a chemical, biochemical or biological reaction or the like can be performed in a reaction vessel, and then the reaction solution can be used as a rotor to perform a centrifugal separation process to perform solid-liquid separation.
  • the reaction apparatus of the present invention since the supernatant liquid can be discharged out of the system after solid-liquid separation of the reaction liquid, a conventional apparatus for separately removing the supernatant liquid after centrifugation treatment This is much more convenient than
  • the reaction apparatus of the present invention can be suitably applied not only to chemical reactions but also to chemical reactions in a broad sense including biochemical and biological reactions.
  • the reaction apparatus of the present invention can perform centrifugation, the reaction solution after the reaction can be directly solid-liquid separated by centrifugation, and the supernatant separated by the centrifugation can be used. Can be discharged out of the system with higher centrifugal force.
  • reaction apparatus of the present invention can be suitably applied particularly to biochemical reactions, and in particular, can be suitably applied to perfusion culture of biological cells (particularly animal cells).
  • the culture solution to be subjected to centrifugation is not particularly limited, but those obtained by suspension culture with suspension cells, cells that proliferate by forming aggregates such as iPS cells, cells fixed on suspension carriers, etc. Is preferred.
  • a reaction in which a solid is generated by a chemical reaction is very preferable because solid-liquid separation can be performed as it is by a centrifugal separation function.
  • a reaction involving the generation of crystals can be performed in a reaction vessel, and the crystals can be recovered by centrifugation.
  • microorganisms or biological cells can be cultured in a reaction vessel, and then the liquid culture can be separated into solid and liquid by centrifugation. it can. If solid-liquid separation can be achieved by centrifugation, solid microorganisms and cells separated in the reaction vessel can be repeatedly cultured to facilitate concentration of microorganisms and cells, perfusion culture, etc. It is possible to collect and recover useful components efficiently.
  • perfusion culture can be carried out in a preferred mode of use.
  • a so-called perfusion is performed in which a fresh liquid medium containing nutrient components and a liquid medium containing waste components (waste liquid) are exchanged while the animal cells are captured (residual) in the culture tank.
  • waste liquid waste components
  • to maintain cell growth in perfusion culture fragile cells are not mechanically damaged, under physiological conditions, and free of microorganisms (miscellaneous), for example, Cell separation and liquid medium exchange are repeated for a long period of time, such as one month or longer.
  • reaction apparatus of the present invention there is no need to transfer the reaction solution after the reaction to a centrifuge, so that the culture solution after perfusion culture is used as it is in the reaction apparatus of the present invention for solid-liquid separation and overflow of the supernatant liquid. Can be discharged outside the system.
  • the rotation speed is adjusted by centrifugation to adjust the inside of the reaction container. Crystals can be settled on the wall surface, a reaction solution containing microorganisms can be taken out as a supernatant into the housing, and the reaction solution containing the microorganisms can be recovered and used again for the reaction.
  • the cells to be used are not particularly limited as long as they are biological cells, and plant cells and animal cells can be used.
  • various pluripotent stem cells such as embryonic stem cells (ES cells), induced pluripotent stem cells (iPS cells), hybridomas, cancer cells, lymphocyte cells, etc. may be used as animal cells as appropriate. it can.
  • ES cells embryonic stem cells
  • iPS cells induced pluripotent stem cells
  • hybridomas cancer cells
  • lymphocyte cells etc.
  • the cells may be cultured by a conventional method under conditions suitable for culturing the culture.
  • the reaction apparatus of the present invention can easily adjust the conditions in the reaction vessel. Cell culture and the like can also be suitably carried out.
  • the reaction apparatus of the present invention is a reaction apparatus that also serves as a centrifuge, but the reaction apparatus of the present invention includes a bottomed cylindrical reaction vessel having an upper portion opened at a peripheral edge, and the reaction vessel.
  • a substantially cylindrical housing accommodated in the interior; and a drive unit disposed on the outside of the housing for driving the reaction vessel to rotate about the axis via an axial axis.
  • the reaction container is rotated by the drive unit, and the centrifugal separation process is performed. Then, by further increasing the rotation speed of the reaction vessel, the supernatant of the reaction solution overflowing from the peripheral edge of the open end of the upper portion of the reaction vessel is received by the housing.
  • the supply of the internal solution to the reaction vessel may be performed by an appropriate method, for example, pouring with a vessel or pouring with a pump, by removing the upper cover of the housing.
  • the supernatant liquid overflowing in the housing may be performed by an appropriate method, for example, a method of sucking and collecting with a suction pump.
  • the reaction apparatus of the present invention comprises a supply pipe for supplying the content liquid to the reaction vessel at the upper part of the housing (upper lid (top plate) or upper side surface (side wall)), and a lower part of the housing.
  • a discharge pipe for discharging the supernatant liquid of the reaction liquid overflowing from the peripheral edge of the open end of the upper part of the reaction vessel to the outside of the housing can be provided on the side surface or the bottom surface.
  • the content liquid supply pipe is provided in the reaction container from the upper lid or the upper side surface of the housing to which the base is fixed, and is disposed so as not to prevent the reaction container from rotating during the centrifugation process. It is said to be length.
  • the supply pipe communicates with a supply source of content liquid to be subjected to the reaction in the reaction vessel via liquid supply means such as an on-off valve and a pump.
  • the supply pipe is connected to a supply source of a cleaning liquid for cleaning the separated solid via a direction switching valve or the like, and the tip of the supply pipe is bent at the time of cleaning.
  • the solid can be washed by, for example, directing toward the inner wall of the reaction vessel.
  • the overflowed supernatant can be discharged out of the system naturally by providing the discharge pipe at the lower part (lower side or bottom surface) of the housing.
  • forcible discharge may be performed by connecting a pump or the like to the discharge pipe.
  • the material of the reaction vessel and the housing is not particularly limited, and metal, synthetic resin, glass, etc. are used.
  • a material transparent to the side surface (side wall), the side surface of the housing, the upper lid, etc., such as polycarbonate, is preferably used.
  • the volume of the reaction vessel is not particularly limited, but can be, for example, 30 mL to 1000 L.
  • the reaction container 2 of the present invention in the reaction apparatus 1 of the present invention has a bottomed cylindrical shape, the upper part is opened at the peripheral edge, and the supernatant liquid of the reaction liquid separated by solid-liquid separation by centrifugation. Overflows into the housing 3 from the peripheral edge of the upper opening end (FIG. 1A).
  • the reaction vessel 2 of the present invention may be provided with an inner rim 2c at the peripheral edge of the upper opening end.
  • the centrifugal force is increased during the centrifugal separation process. It becomes easy to control the amount of the supernatant of the reaction solution that overflows (FIG. 1B). That is, if there is no rim portion as shown in FIG. 1A, the supernatant liquid overflows from the peripheral edge of the upper open end of the reaction vessel 2 in a state where the solid-liquid separation is not sufficiently performed during the centrifugation process.
  • FIG. 1B the reaction vessel 2 of the present invention may be provided with an inner rim 2c at the peripheral edge of the upper opening end.
  • the solid-liquid separation is sufficiently performed by a centrifugal separation process in which the rotational speed of the drive unit (the rotational speed of the reaction vessel) is increased. Is further raised to allow the supernatant to overflow from the peripheral edge of the upper opening end (the opening end inside the rim 2c).
  • the volume of the reaction liquid (L 1 ) in the reaction vessel is the outer edge at the rim portion in the reaction vessel (
  • the capacity (L 2 ) of the annular columnar portion occupied by the width between the inner surface) of the reaction vessel and the inner edge and the height of the reaction vessel is set (large). By doing so, it becomes easy to overflow the supernatant liquid of the solid separation by the centrifugal separation process.
  • the relationship between the reaction vessel and the amount of the reaction liquid according to the present invention is L 2 ⁇ L 1 , but L 2 is as shown in the following equation.
  • the supernatant liquid is placed on the side surface by providing horizontal slits (gap) at appropriate intervals at appropriate height positions on the side surface connected to the outer edge of the rim portion of the reaction container. It can also overflow.
  • the presence or absence of the rim portion can be selectively used depending on the properties of the reaction solution, for example, by closing the slit with an appropriate covering member from the inside or the outside of the reaction vessel so as to have no rim portion.
  • the reaction vessel in the reaction apparatus of the present invention is not particularly limited as long as it is set so as to be rotatable about an axis via an axis in the axial direction in relation to a housing that accommodates the reaction vessel.
  • reaction vessel 2 of the present invention can be rotatably attached to a column shaft 3e that rises from the substantially central portion of the bottom in the housing 3 (FIG. 2A).
  • a hollow tube portion that rises from a central portion of the bottom portion in the reaction vessel 2 and has a column tube 3e that rises from a substantially central portion of the bottom portion in the housing 3 and opens to the outside of the bottom portion.
  • the reaction vessel 2 can be rotatably mounted around the axis via a bearing provided at the upper end of the hollow tube portion by being inserted into the (cylindrical tube portion).
  • the reaction vessel is driven to rotate at a position where the reaction vessel 2 faces the permanent magnets 2f1 and 2f2 disposed horizontally on the bottom of the reaction vessel 2 and the permanent magnets 2f1 and 2f2.
  • Driving permanent magnets 4c1, 4c2 having a polarity different from that disposed horizontally near the bottom of the outer side of the housing 3, and the driving unit 4 connected to the driving permanent magnets 4c1, 4c2 via a driving rotary shaft; Is driven to rotate (FIG. 2A).
  • the upper lid 3b of the housing 3 can be removed, and the reaction vessel 2 can be removed from the inside and taken out of the housing 3, which is more preferable from the viewpoint of washing the reaction vessel 2 and the like. It is.
  • reaction vessel 2 of the present invention has one end of the drive rotation shaft connected to the center of the bottom of the reaction vessel 2 and the other end via a bearing (radial bearing) at the bottom of the housing 3. Then, it is connected to the drive unit 4 and driven to rotate (FIG. 2B).
  • the reaction vessel 2 of the present invention has one end of a rotating shaft for the reaction vessel 2 connected to the center of the bottom of the outer side of the reaction vessel 2 and the other end bearing of the bottom of the inside of the housing 3.
  • a permanent magnet 2f3, 2f4 that is rotatably connected to the (thrust bearing) and is disposed horizontally with respect to the rotation shaft, and horizontally in the vicinity of the bottom of the housing 3 at a position facing the permanent magnets 2f3, 2f4.
  • the drive permanent magnets 4c1 and 4c2 having different polarities from that of the arranged permanent magnets 4c1 and 4c2 and the drive unit 4 connected to the drive permanent magnets 4c1 and 4c2 via a drive rotation shaft are rotationally driven (FIG. 2C).
  • the reaction vessel 2 of the present invention is rotationally driven by the drive unit 4 arranged outside the upper lid of the housing 3 (FIG. 2D). That is, the reaction vessel 2 has one end of the drive rotating shaft connected to the drive unit 4 arranged outside through the lid of the upper portion of the housing 3 through a bearing if necessary, and the other end is connected to the inside of the reaction vessel 2. It is rotationally driven by hanging and connecting to the center of the bottom of the.
  • the reaction apparatus of the present invention may include a stirring apparatus.
  • the stirring device includes a drive unit 5a disposed on the lid 3b on the top of the housing 3 and a rotating shaft for stirring suspended in the reaction vessel 2 connected to the drive unit 5a and rotating via a bearing if necessary. 5b1 and a stirring blade 5c1 attached in the vicinity of the lower part (FIG. 3A).
  • the arrangement of the drive unit 5a with the lid 3b on the top of the housing 3 is usually located at a substantially central portion of the reaction vessel 2, it may be eccentric.
  • the reaction apparatus 1 of the present invention is configured such that the drive of the reaction vessel 2 is driven via a drive rotary shaft whose one end is connected to the bottom of the reaction vessel 2 as shown in FIG. 2B. 4, the rotating shaft 5b2 for stirring suspended inside the reaction vessel 2 via the bearing of the lid 3b at the top of the housing 3, and the stirring blade 5c2 attached in the vicinity of the lower portion.
  • a stirrer FIG. 3B
  • the agitating blade 5c2 rotates in the vicinity of the bottom of the housing 3 at a position facing the permanent magnets 5d1, 5d2 for blades disposed horizontally on the agitating blade 5c2 and the permanent magnets 5d1, 5d2 for blades.
  • the wing permanent magnets 5d1 and 5d2 arranged horizontally on the body and the wing drive permanent magnets 6a1 and 6a2 having different polarities, and the wing drive unit for rotating the rotator via a rotation transmission means, for example, a belt or the like It is rotationally driven by (motor) 6 (FIG. 3B).
  • the rotating body is rotatably attached to a driving rotating shaft that connects the bottom portion outside the reaction vessel 2 and the driving unit 4.
  • the rotational drive of the reaction vessel 2 is a rotation that is rotatably attached to a drive rotary shaft connected to the bottom of the reaction vessel 2 and the drive unit 4. Since the body is free of rotation with respect to the drive rotation shaft and remains in a stopped state without rotating, the body is made by the drive unit 4 via the drive rotation shaft.
  • the reaction apparatus 1 of the present invention suspends the liquid flow baffle member 7 from the lid 3b on the top of the housing 3 so that a part of the liquid flow baffle member 7 is submerged in the content liquid inside the reaction vessel 2. Then, the content liquid can be stirred by rotating the reaction vessel 2 around the axis at a speed suitable for stirring the content liquid (FIG. 3C).
  • liquid flow baffle member 7 examples include various sensors, baffle plates, rod-like or tubular members (example: liquid supply pipe for supplying a pH adjusting liquid such as acid or alkali, heat exchange for heating or cooling) Pipe) and the like, and at least one of them is used.
  • the low-speed rotation drive of the reaction vessel 2 for stirring the content liquid and the high-speed rotation drive for the centrifugal separation are performed by rotating the drive unit 4 with a speed setting device or the like (for example, 50 rpm). Etc.) and high-speed rotation (for example, 1500 rpm, etc.), respectively.
  • the liquid flow baffle member 7 is simply suspended in the reaction vessel 2 from the lid 3b at the top of the housing 3, and the reaction solution 2 can be rotated at low speed to agitate the content liquid. It is possible and suitable.
  • the rotational speed of the reaction vessel is usually gradually increased, and the reaction solution is moved in the lateral direction in the reaction vessel by centrifugal force.
  • the position below it is sufficient that it is arranged in a range that does not come into contact with the reaction solution during the centrifugation process.
  • reaction apparatus of the present invention may be provided with means for maintaining and managing the reaction conditions and environment.
  • maintenance / management means such as reaction conditions are attached, for example, through the lid on the upper part of the housing, as necessary, in an airtight manner, or as detachable as necessary.
  • Such means include at least the above-mentioned various sensors (dissolved oxygen concentration, pH, temperature), baffle plate, liquid supply pipe, heat exchange pipe, etc., gas supply pipe (sparger), exhaust pipe, etc. One is preferably used. In addition, a septum for sampling or the like may be provided if necessary.
  • reaction apparatus of the present invention may be provided with temperature adjusting means such as a heater and / or a cooler outside the housing in order to adjust reaction conditions such as temperature.
  • temperature adjusting means such as a heater and / or a cooler outside the housing in order to adjust reaction conditions such as temperature.
  • the reaction vessel and the housing can be appropriately disassembled and assembled so that handling, washing, etc. are facilitated.
  • the bottom of the reaction container and the top and bottom of the housing can be detachable by screwing or the like.
  • the content liquid is supplied into the reaction vessel through a supply pipe communicating with the supply source, and the reaction is performed while rotating the reaction vessel at a low speed as required under the necessary reaction conditions.
  • a supply pipe communicating with the supply source communicating with the supply source
  • the reaction is performed while rotating the reaction vessel at a low speed as required under the necessary reaction conditions.
  • what is necessary is just to insert suitably from the insertion port of a housing upper part, when there exists an additive to a content liquid.
  • the method such as centrifugal separation of the reaction solution after the reaction can be performed so that the solid-liquid separation of the reaction solution and the overflow of the supernatant from the peripheral edge of the open end of the upper part of the reaction vessel are performed by centrifugal force.
  • the conditions may be adjusted as appropriate. For example, by gradually increasing the number of revolutions of the reaction vessel, solid-liquid separation is performed at a number of revolutions at which the reaction solution does not overflow from the peripheral edge of the upper opening end of the reaction vessel, and then the supernatant is separated by further increasing the number of revolutions. May be allowed to overflow from the peripheral edge.
  • the relationship between the rotational speed of the reaction vessel, the solid-liquid separation state, and the overflow state of the supernatant is obtained in advance, and operations such as centrifugation are performed based on this relationship.
  • the number of rotations of the reaction vessel may be appropriately adjusted and set according to the properties of the reaction solution, but the number of rotations at the time of solid-liquid separation and overflow of the supernatant liquid is at the open end of the reaction vessel.
  • the speed may be 500 to 1500 rpm.
  • the number of revolutions of the reaction vessel can be made higher than that in FIG. 1A, and solid-liquid separation is more effective.
  • the number of rotations depends on the properties of the reaction solution, but can be, for example, 500 to 3000 rpm.
  • FIG. 4 is a view showing an embodiment of the reaction apparatus of the present invention
  • FIG. 4A is a top view thereof
  • FIG. 4B is a longitudinal sectional view thereof.
  • the reaction apparatus 11 of the present invention also serves as a centrifuge, and has a bottomed cylindrical reaction vessel 12 whose upper part opens at the peripheral edge, and a substantially cylinder that accommodates the reaction vessel 12 therein. And a drive unit (motor) 14 that is disposed in the vicinity of the bottom of the outer side of the housing 13 and rotates the reaction vessel 12 around the axis via an axis in the axial direction.
  • a drive unit (motor) 14 that is disposed in the vicinity of the bottom of the outer side of the housing 13 and rotates the reaction vessel 12 around the axis via an axis in the axial direction.
  • reaction vessel 12 is formed by watertightly screwing the first cylindrical member (side surface) 12a to the first bottom member 12b via an O-ring at the lower end thereof.
  • an inner rim portion (inner collar portion) 12c is fixedly provided on the peripheral edge portion of the upper opening end of the reaction vessel 12.
  • a hollow tube portion (cylindrical tube portion) that opens to the outside of the bottom portion for inserting a column shaft 13e that rises from the bottom portion of the housing 13 to be described later is inserted into the center portion of the first bottom member 12b in the reaction vessel 12.
  • 12d stands up integrally from the first bottom member, and a bearing 12e of the support shaft 13e is attached to the upper end thereof.
  • permanent magnets 12f1 and 12f2 are built in the first bottom member 12b (the bottom portion outside the reaction vessel 12).
  • the housing 13 for containing the reaction vessel 12 is formed by screwing a lid (top plate) 13b on the upper end of the second cylindrical member (side surface) 13a with a cap nut 13c in a watertight manner through an O-ring.
  • a second bottom member 13d is formed at the lower end by watertight screwing through an O-ring.
  • a supply pipe S1, a temperature sensor insertion sheath pipe S2, an exhaust pipe S3, and the like communicating with a reaction solution supply source are provided in the lid 13b on the upper portion of the housing 13, if necessary. Or it is attached detachably.
  • the sheath tube S2 hanging from the lid 13b at the top of the housing 13 into the content liquid functions as a liquid flow obstruction object by rotating the reaction vessel 12 at a rotation speed suitable for stirring during the reaction. Can play.
  • the lid 13b at the top of the housing 13 includes various sensors S4 and S5, a liquid supply pipe S6 such as acid and alkali for pH adjustment, a gas supply pipe S7 for aeration and stirring, and a sampling port. S8 and the like can be provided as appropriate.
  • a support shaft 13e whose base is fixed to the second bottom member in a watertight manner with an adhesive or the like rises, and this support shaft 13e is a reaction vessel.
  • the reaction vessel 12 is inserted into the hollow portion of the 12 hollow tube portions 12d, and is supported rotatably and detachable by the tip of the support shaft 13e and the bearing 12e.
  • a sliding bearing (metal) is provided on the sliding portion between the inner surface of the lower end of the hollow tube portion 12d of the reaction vessel 12 and the support shaft 13e of the housing 13, so that the reaction vessel 12 can be driven smoothly. Done.
  • the bottom of the housing 13 has a discharge pipe 13f for discharging the supernatant to the outside.
  • a drive unit (motor) 14 that rotationally drives the reaction vessel 12 via a support base P is provided in the vicinity of the bottom of the outer side of the housing 13, and a rotation mounted horizontally on a drive rotary shaft 14 a connected thereto.
  • Driving permanent magnets 14c1 and 14c2 having different polarities from the permanent magnets 12f1 and 12f2 are disposed on the panel 14b.
  • the drive part 14 can be switched to the high speed rotation for the low speed rotation of the reaction container 12 for the stirring of the content liquid, the centrifugation process, etc. using a speed setting device etc.
  • the content liquid to be used for the reaction is introduced into the reaction vessel 12 through the supply pipe S1, and the reaction is performed under appropriate conditions. Separation process is performed for solid-liquid separation, and the separated supernatant is overflowed from the peripheral edge of the rim portion 12c at the upper opening end of the reaction vessel 12 by further increasing the rotational speed of the container, and if necessary The supernatant liquid is discharged to the outside of the housing 13 through the discharge pipe 13f.
  • the supernatant obtained by solid-liquid separation of the reaction solution by centrifugal separation is allowed to overflow from the peripheral edge of the upper open end of the reaction vessel while preventing solid mixing and outflow. Therefore, it is particularly effective for the concentration of microorganisms and animal and plant cells, perfusion culture, and the like.
  • the materials of the reaction vessel 12 and the housing 13 are not particularly limited.
  • the first cylindrical member 12a and the rim portion 12c of the reaction vessel 12 for example, polycarbonate resin (PC) or the like is used in the first bottom member 12b.
  • PC polycarbonate resin
  • stainless steel or the like is preferably used for the bearing 12e, for example, polyphenylene sulfide resin (PPS).
  • the second cylindrical member 13a and the upper lid 13b of the housing 13 for example, PC or the like is suitably used, and in the second bottom member 13d and the column shaft 13e, for example, stainless steel or the like is suitably used.
  • reaction apparatus of the present invention when the reaction apparatus of the present invention is applied to microorganisms, animal and plant culture, etc., it is preferable to use a heat-resistant material in consideration of steam heat sterilization and the like.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Centrifugal Separators (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Mixers Of The Rotary Stirring Type (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

La présente invention aborde le problème de fourniture d'un dispositif de réaction qui sert également de centrifugeuse de manière à pouvoir conduire efficacement une séparation solide-liquide par centrifugation, et dans lequel une cuve de réaction présente une structure interne simple. La présente invention concerne un dispositif de réaction qui sert également de centrifugeuse qui est pourvu de : une cuve de réaction cylindrique à fond fermé ayant une partie supérieure qui s'ouvre à la périphérie ; un boîtier sensiblement cylindrique pour loger la cuve de réaction à l'intérieur de celui-ci ; et une unité d'entraînement pour, au moyen d'un arbre, entraîner en rotation la cuve de réaction autour de l'axe de l'arbre. Une fois qu'un contenu liquide devant être soumis à une réaction a réagi dans la cuve de réaction, la cuve de réaction est entraînée en rotation autour de l'axe pour effectuer une séparation solide-liquide sur un liquide de réaction par force centrifuge et causer le débordement d'un liquide surnageant depuis une extrémité d'ouverture au niveau de la partie supérieure de la cuve de réaction.
PCT/JP2016/054671 2016-02-18 2016-02-18 Dispositif de réaction pour effectuer une centrifugation WO2017141394A1 (fr)

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PCT/JP2016/054671 WO2017141394A1 (fr) 2016-02-18 2016-02-18 Dispositif de réaction pour effectuer une centrifugation
JP2017506945A JPWO2017141394A1 (ja) 2016-02-18 2016-02-18 遠心分離可能な反応装置

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PCT/JP2016/054671 WO2017141394A1 (fr) 2016-02-18 2016-02-18 Dispositif de réaction pour effectuer une centrifugation

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CN109127165A (zh) * 2018-10-26 2019-01-04 镇江龙成绝缘材料有限公司 一种用于生产高性能特征聚酰亚胺复合材料的离心机
WO2020138506A1 (fr) * 2018-12-27 2020-07-02 エイブル株式会社 Appareil de culture pour perfusion et séparateur centrifuge
JP2020141579A (ja) * 2019-03-05 2020-09-10 エイブル株式会社 灌流培養システム及び遠心機
CN111676128A (zh) * 2020-07-01 2020-09-18 西藏自治区农牧科学院畜牧兽医研究所 一种牛羊瘤胃液生产发酵罐及其制作方法
CN113303591A (zh) * 2021-06-01 2021-08-27 杭州卓冠教育科技有限公司 一种数字书法临摹桌

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JPS54126675A (en) * 1978-02-21 1979-10-02 Ici Ltd Chemical method on surface of rotating article
JPS6398742A (ja) * 1986-10-15 1988-04-30 Matsushita Electric Works Ltd 入力ノイズ吸収機能を有するシ−ケンサ
JPH0576344A (ja) * 1991-09-20 1993-03-30 Hitachi Ltd 浮遊性細胞の培養方法及び培養装置
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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109127165A (zh) * 2018-10-26 2019-01-04 镇江龙成绝缘材料有限公司 一种用于生产高性能特征聚酰亚胺复合材料的离心机
CN109127165B (zh) * 2018-10-26 2024-05-24 镇江龙成绝缘材料有限公司 一种用于生产高性能特征聚酰亚胺复合材料的离心机
WO2020138506A1 (fr) * 2018-12-27 2020-07-02 エイブル株式会社 Appareil de culture pour perfusion et séparateur centrifuge
JP2020103262A (ja) * 2018-12-27 2020-07-09 エイブル株式会社 灌流培養装置及び遠心分離機
JP2020141579A (ja) * 2019-03-05 2020-09-10 エイブル株式会社 灌流培養システム及び遠心機
WO2020179166A1 (fr) * 2019-03-05 2020-09-10 エイブル株式会社 Système de culture à perfusion et centrifugeuse
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CN111676128A (zh) * 2020-07-01 2020-09-18 西藏自治区农牧科学院畜牧兽医研究所 一种牛羊瘤胃液生产发酵罐及其制作方法
CN113303591A (zh) * 2021-06-01 2021-08-27 杭州卓冠教育科技有限公司 一种数字书法临摹桌

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