WO2022142638A1 - 一种大循环细胞截留装置、流体循环泵以及下探式摇床 - Google Patents

一种大循环细胞截留装置、流体循环泵以及下探式摇床 Download PDF

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Publication number
WO2022142638A1
WO2022142638A1 PCT/CN2021/126286 CN2021126286W WO2022142638A1 WO 2022142638 A1 WO2022142638 A1 WO 2022142638A1 CN 2021126286 W CN2021126286 W CN 2021126286W WO 2022142638 A1 WO2022142638 A1 WO 2022142638A1
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Prior art keywords
tank
thermal insulation
shaker
supernatant
bottom plate
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PCT/CN2021/126286
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English (en)
French (fr)
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惠倪
惠识瑶
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惠倪
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Publication of WO2022142638A1 publication Critical patent/WO2022142638A1/zh

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    • 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
    • C12M1/02—Apparatus for enzymology or microbiology with agitation means; with heat exchange means
    • 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
    • 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
    • C12M1/12—Apparatus for enzymology or microbiology with sterilisation, filtration or dialysis means
    • 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 invention relates to the technical field of cell trapping devices, in particular to a large-circulation cell trapping device, a fluid circulation pump and a descending shaker.
  • the world's most used mainstream cell retention devices in addition to using hollow fiber tangential flow filtration technology, all use the unique "pump and push" reciprocating motion of diaphragm pumps to make the cell mixture flow back and forth.
  • the supernatant is extracted by using a peristaltic pump in the outer cavity of the hollow fiber membrane tube, which realizes the key step of culturing cells in the perfusion process - extracting the supernatant and trapping the cells in the reaction tank at the same time.
  • the above method can trap 100% of the cells in the reaction tank, and it is this diaphragm pump that causes the cell mixture to change direction at high frequency (one reciprocation for two seconds) The fluid pressure is changed at the same frequency, causing damage to the cells.
  • the flow direction of the cell mixture is parallel to the centerline of the hollow fiber tube, and the cell mixture is drawn in and pushed out parallel to the centerline of the hollow fiber tube.
  • the direction of flow in and out is opposite.
  • the peristaltic pump draws out the supernatant
  • the area of the outer cavity of the hollow fiber tube is negative pressure, so that some cells in the cell mixture flowing in the hollow fiber membrane tube are also affected by the negative pressure of the outer cavity of the hollow fiber membrane tube.
  • the supernatant flows out of the tube together, and when the cells reach the micropores on the inner wall of the hollow fiber membrane tube, a small amount of cells are blocked on the micropores, and are not carried down by the mixed liquid flowing down in the tube.
  • the purpose of the present invention is to provide a large circulation cell trapping device, a fluid circulation pump and a descending shaker, so as to solve the technical problems existing in the prior art.
  • the present invention is a descending shaker, comprising: a shaker body;
  • the rocking plate on the top of the rocker body is installed on the upper bearing plate; the four corner positions of the upper bearing plate are respectively installed on the upper ends of the four downwardly probed columns, and the middle of the four downwardly probed columns is installed with a column a fixing frame; the lower ends of the four downwardly probed columns are respectively installed on the bottom plate of the rocking plate; the bottom plate of the rocking plate is installed with a sliding sleeve and a sleeve locking screw, and the sleeve locking screw is installed on the center line of the sliding sleeve Outside; the upper part of the sliding sleeve is equipped with a bottom plate of a thermal insulation tank body and an openable and closable thermal insulation tank body, and the bottom of the thermal insulation tank body and the bottom plate of the rocking plate are reserved for installation ports for pipelines extending vertically downward. .
  • the openable and closable thermal insulation tank includes: a bottom of the thermal insulation tank, a front half of the thermal insulation tank and a rear half of the thermal insulation tank; the bottom of the thermal insulation tank is provided with the front half of the thermal insulation tank and the thermal insulation tank the rear half body; the bottom of the thermal insulation tank body is provided with a sliding seat for being sleeved on the sliding sleeve; the front half of the thermal insulation tank and the rear half of the thermal insulation tank are connected on the rotating side through the thermal insulation tank body hinge; Locking bolts are arranged on the opening and closing sides of the front half of the thermal insulation tank and the rear half of the thermal insulation tank.
  • the bottom plate of the rocking plate is provided with a block on the sliding path of the thermal insulation tank, and the outer side of the bottom plate of the thermal insulation tank has an L-shaped engaging portion;
  • the L-shaped abutting part on the outer side of the body bottom plate is suitable for it.
  • four tank positioning pins are arranged between the front half of the thermal insulation tank and the rear half of the thermal insulation tank.
  • the front and rear halves of the thermal insulation tank are combined to bear the weight together.
  • the descending shaking table in the present invention can meet the fluid mechanics requirements of the circulating pump, and has better effect than the existing traditional shaking table. Because the traditional shaker is provided with the shaker body (the part of the shaker drive mechanism) at the lower part of the shaker, due to structural limitations, there is no space for the pipeline to protrude vertically downward in the middle of the shaker, and the pipeline must be turned and set, so that the The fluid mechanics angle is obviously not as good as the down-type shaking table in this embodiment.
  • the present invention provides a fluid circulation pump, which includes: a double-layer hard plastic shaker, a stirring tank and the above-mentioned descending shaker; the double-layer hard plastic shaker is arranged in an openable and closable heat preservation tank In the body; the upper water outlet of the stirring tank is connected with the two return water ports at the bottom of the inner tank of the double-layer hard plastic shaker through two return water silicone hoses; the lower water inlet of the stirring tank is connected to the The water outlet of the outer tank bottom of the outer tank bottom of the double-layer hard plastic shaker is connected by a water outlet silica gel hose; the stirring tank is provided with a stirring shaft, the stirring shaft is equipped with a stirring paddle, and the end of the stirring shaft is Motor is installed.
  • the double-layer hard plastic shaker includes: an outer tank, an inner tank and a tank cover; the bottom center of the outer tank is provided with an outer tank bottom water outlet;
  • the outer tank is in the shape of a conical tank, and the lower part of the outer tank is in the shape of a drum tank;
  • the outer tank is symmetrically provided with two water inlet protrusions on the upper conical tank;
  • the bottom of the outer tank is provided with four positioning
  • the outer tank bottom water outlet at the bottom of the outer tank can protrude vertically downward from the installation holes reserved for the bottom plate of the thermal insulation tank body and the bottom plate of the rocking plate;
  • the bottom of the inner tank is symmetrically arranged with two water outlet;
  • the upper part of the inner tank is in the shape of a conical tank, and the lower part of the inner tank is in the shape of a drum tank;
  • the inner tank is provided with an inner tank water outlet symmetrically at the position of the upper conical tank body;
  • the inner tank is inserted inside the outer tank, and the bottom of the inner tank is provided with a positioning seat, and the positioning seat is inserted and connected to the positioning column at the bottom of the outer tank.
  • any one of the water outlet silica gel hose and the two return water silica gel hoses is provided with a hollow fiber microfiltration membrane column; the hollow fiber microfiltration membrane column is connected to the The mixing tank is connected.
  • the fluid circulation pump includes: a movable bracket; the movable bracket includes: a bracket, a movable bracket bottom plate, and four moving wheels of the movable bracket; the top of the bracket is provided with a pipe clamp, The tube clip is used to install the support shaft of the downward rocker, and the shaker body is installed on the support shaft of the downward rocker; the lower part of the bracket is provided with a movable bracket bottom plate; the bottom of the bracket is provided with There are movable brackets with four wheels.
  • the cell mixture flows in one direction in the large circulation loop inside the stirring tank and inside and outside the double-layer hard plastic shaker, with stable flow rate, no frequency, and high-speed repetition of direction and pressure. Changes, the cell damage is very small (because the animal cell itself has no cell wall, only a thin cell membrane, a small shear force can break the cell membrane and cause cell death). Moreover, in the process of cell retention, due to the oscillating motion of the mixed liquid in the double-layer hard plastic shaker, the effect of water splashes and water droplets is raised, which greatly increases the surface area of the gas-liquid ratio in the shaker, thereby greatly increasing the dissolution rate. The oxygen level and speed also greatly improves the speed of removing harmful gases such as carbon dioxide and ammonia in the mixed liquid, and has the purification function of increasing oxygen and discharging harmful gases. At present, the existing cell retention devices in the world do not have these two functions.
  • the present invention also provides a large circulating cell retention device, which includes: a supernatant extraction and backwashing system and the above-mentioned fluid circulation pump;
  • the supernatant extraction and backwashing system includes: a hollow fiber microfiltration system Membrane column, peristaltic pump, diaphragm pump assembly, heat preservation tank, supernatant liquid turnover bag, supernatant liquid storage bag and supernatant liquid storage tank;
  • the upper part of the hollow fiber microfiltration membrane column has a supernatant liquid extraction outlet, and the There is a supernatant backwash inlet at the bottom of the hollow fiber microfiltration membrane column; one end of the peristaltic pump hose of the peristaltic pump is connected to the supernatant outlet, and the other end of the peristaltic pump hose of the peristaltic pump is connected to the supernatant.
  • the upper part of the turnover bag is connected, and the lower part of the supernatant turnover bag is connected with the diaphragm pump assembly; the middle part of the supernatant turnover bag is connected with the supernatant storage bag in the supernatant storage tank; the diaphragm pump The assembly is connected to the supernatant backwash inlet.
  • the cell mixture flows in a single direction in the large circulation loop inside the stirring tank and the double-layer hard plastic shaking tank, with stable flow rate, no frequency, high-speed repeated changes of direction and pressure, and great cell damage.
  • Small because animal cells themselves have no cell wall, only a thin cell membrane, a small shear force can break the cell membrane and cause cell death).
  • the cell concentration of the cell mixture is always the same as the cell concentration of the cell mixture in the stirring tank, the supernatant does not increase the concentration when the supernatant is extracted, and the extraction is easy .
  • the volume of the shaking tank can be increased, the diameter of the circulation pipeline can also be increased, and the shaking speed can also be increased.
  • the flow rate can also be very high.
  • the volume of the shaker is 20 liters
  • the rotation speed is 80 revolutions per minute
  • the flow measurement is 4 times the volume, that is, 80 liters per minute.
  • the volume of the shaking tank of the present invention can be enlarged to 200 liters or even 500 liters, which far exceeds the flow rate of the existing cell trapping devices in the world. In this way, the larger the circulating flow rate, the higher the dissolved oxygen level and the faster the dissolved oxygen speed.
  • the present invention can better satisfy the large-volume and high-density large-scale animal cell culture.
  • Fig. 1 is the side view of the descending shaker provided by the first embodiment of the present invention
  • Fig. 2 is the top view of the descending type shaking table provided by the first embodiment of the present invention
  • Fig. 3 is the top view of the in-situ state of the downward rocking table provided in the first embodiment of the present invention
  • Fig. 4 is the top view of the state where the dip-type shaking machine is pulled out of the thermal insulation tank provided by the first embodiment of the present invention
  • Fig. 5 is the top view of the state in which the dip-down shaker provided in the first embodiment of the present invention opens the thermal insulation tank and is loaded into the double-layer hard plastic shaker;
  • Fig. 6 is the top view of the state where the descending shaker according to the first embodiment of the present invention is closed with the thermal insulation tank body, pushed back into the thermal insulation tank body, and locked in the working position;
  • Embodiment 7 is a side view of the fluid circulation pump provided in Embodiment 1 of the present invention.
  • Embodiment 8 is a side view of a double-layer hard plastic shaker provided in Embodiment 1 of the present invention.
  • Fig. 9 is the top view of the double-layer hard plastic shaker provided in the first embodiment of the present invention.
  • FIG. 10 is a side view of the movable bracket provided in Embodiment 1 of the present invention.
  • FIG. 11 is a top view of the movable bracket according to Embodiment 1 of the present invention.
  • FIG. 12 is a side view of the macrocirculatory cell trapping device provided in Embodiment 1 of the present invention.
  • FIG. 13 is a side view of the supernatant extraction and backwashing system provided in Embodiment 1 of the present invention.
  • the first embodiment provides a drop-down shaker, which includes: a shaker body 202 ; the shaker body 202 is installed on the drop-down shaker support shaft 220 .
  • the rocking plate 208 on the top of the rocker body 202 is installed on the upper bearing plate 210; the four corner positions of the upper bearing plate 210 are respectively installed on the upper ends of the four downwardly probed columns 214, and the four downwardly probed columns
  • a column fixing frame 216 is installed in the middle of the 214; the lower ends of the four downwardly probed columns 214 are respectively installed on the rocking plate bottom plate 218;
  • the sleeve locking screw 322 is installed on the outside of the center line of the sliding sleeve 320; the sliding sleeve 320 is slidably installed with a heat preservation tank body that can be opened and closed, and a space between the bottom of the heat preservation tank body and the bottom plate 218 of the rocking plate is reserved.
  • the installation port extending vertically downward for the pipeline meets the fluid mechanics requirements of the circulating pump, which is better than the existing traditional shaking table. Because the traditional shaker is provided with the shaker body (the part of the shaker drive box) at the lower part of the shaker, due to structural limitations, there is no space for the pipeline to protrude vertically downward in the middle of the shaker, and the pipeline must be bent and arranged so that the The fluid mechanics angle is obviously not as good as the down-type shaking table in this embodiment.
  • the specific form of the shaker body 202 is not limited, and reference may be made to the prior art.
  • the shaker body 202 includes: a shaker drive box (installed eccentrically, with reference to the eccentricity 206 shown in the figure); a drive motor is installed in the shaker drive box; a small pulley is installed on the power output shaft of the drive motor; the The small pulley and the large pulley are connected by belt tension; the large pulley is installed on the active eccentric shaft; the upper end of the active eccentric shaft is connected to the upper rocking plate; the upper rocking plate is connected to four sets of driven shafts; the The upper rocking plate is connected to the rocking plate 208 by bolts, and the rocking plate 208 is mounted on the upper bearing plate 210 .
  • a shaker drive box installed eccentrically, with reference to the eccentricity 206 shown in the figure
  • a drive motor is installed in the shaker drive box
  • a small pulley is installed on the power output shaft of the drive motor
  • the The small pulley and the large pulley are connected by belt tension
  • the large pulley is installed on the active eccentric
  • the upper bearing plate 210 is fixed on the rocking plate 208 , and four descending columns 214 are installed downwardly under the upper bearing plate 210 , and the lower end of the descending columns 214 is equipped with a rocking plate bottom plate. 218.
  • a column fixing frame 216 is installed on the upper half of the four columns to ensure the rigidity and stability of the frame; a sliding sleeve 320, a sleeve locking screw 322 and a stopper 312 are installed on the bottom plate 218 of the rocking plate, and the two sliding sleeves 320 are installed on top
  • the bottom plate 340 of the thermal insulation tank is mounted on the thermal insulation tank which can be divided into two halves, and the installation of the equipment is completed.
  • the openable and closable thermal insulation tank includes: a bottom plate 340 of a thermal insulation tank, a front half of the thermal insulation tank 301 and a rear half of the thermal insulation tank 300; the thermal insulation tank
  • the bottom plate 340 of the tank body is provided with the front half body 301 of the heat preservation tank and the rear half body 300 of the heat preservation tank; the bottom of the bottom plate 340 of the heat preservation tank body is provided with a sliding seat 321 for fitting on the sliding sleeve 320;
  • the front half of the heat preservation tank The body 301 and the rear half body 300 of the thermal insulation tank are connected on the rotating side through the thermal insulation tank body hinge 330; the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank are provided with locking bolts 350 on the opening and closing side.
  • the bottom plate 340 of the thermal insulation tank body is provided with a U-shaped installation port.
  • the bottom plate 218 of the rocking plate is also provided with a U-shaped installation opening.
  • a space for accommodating the double-layer hard plastic shaker 400 is formed between the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank.
  • the maximum opening and closing angle between the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank can be set to 79°.
  • the bottom plate 218 of the rocking plate is provided with a stopper 312 on the sliding path of the thermal insulation tank, and the outer side of the bottom plate 340 of the thermal insulation tank has an L-shaped engaging portion;
  • the L-shaped latching portion on the outer side of the bottom plate 340 of the thermal insulation tank body is adapted to fit.
  • tank positioning pins 303 are arranged between the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank.
  • the second embodiment provides a fluid circulation pump on the basis of the above-mentioned first embodiment.
  • the fluid circulation pump includes: a double-layer hard plastic shaker 400 , a stirring tank 102 , and the descending shaker 200 described in the first embodiment.
  • the double-layer hard plastic shaker 400 is set in a heat-insulating tank body that can be opened and closed;
  • the water return ports 420 are connected by two return water silicone hoses 421;
  • the water outlet 410 at the bottom of the outer tank 414 of the double-layer hard plastic shaker 400 passes through the water outlet at the bottom of the mixing tank 102 and the bottom of the outer tank 414.
  • Silicone hose 411 is connected. It is explained that the static liquid level of the fluid circulation pump is located above the upper water outlet of the stirring tank and below the water outlet of the inner tank.
  • the fluid circulation pump uses a downward-penetrating shaker as the motive force to shake the double-layer rigid plastic shaker clockwise (450 degrees in the clockwise direction), and is connected to the stirring tank, so that the mixed culture fluid circulates in the shaking tank, the stirring tank and the pipeline; the The fluid circulation pump is mounted on the movable bracket through the support shaft of the descending shaker.
  • a stirring shaft 108 is provided in the stirring tank 102 , a stirring paddle 120 is installed on the stirring shaft 108 , and a motor 110 is installed on the end of the stirring shaft 108 .
  • any one of the water outlet silica gel hose 411 and the two return water silica gel hoses 421 is provided with a hollow fiber microfiltration membrane column 500; the hollow fiber microfiltration membrane column 500 is connected to the stirring through a fixing clip Tank 102 is connected.
  • the double-layer hard plastic shaker 400 includes: an outer tank 414, an inner tank 405 and a tank cover 402; the bottom center of the outer tank 414 is provided with an outer tank bottom water outlet 410; The upper part of the outer tank 414 is in the shape of a conical tank, and the lower part of the outer tank 414 is in the shape of a drum tank; the outer tank 414 is symmetrically provided with two water inlet protrusions 422 at the position of the upper conical tank; The bottom of the outer tank 414 is provided with four positioning posts 425; the outer tank bottom water outlet 410 at the bottom of the outer tank 414 can be perpendicular to the mounting holes reserved for the bottom plate 340 of the thermal insulation tank and the bottom plate 218 of the rocking plate.
  • the bottom of the inner tank 405 is symmetrically provided with two water return ports 420; the upper part of the inner tank 405 is in the shape of a conical tank, and the lower part of the inner tank 405 is in the shape of a drum;
  • the tank 405 is provided with an inner tank water outlet symmetrically at the position of the upper conical tank body; one side edge of the inner tank water outlet is provided with an inner tank water outlet tangential flow baffle 461; the bottom side edge of the inner tank water outlet A horizontal flow baffle 462 at the lower part of the water outlet of the inner tank is provided; the two water return ports 420 at the bottom of the inner tank 405 can extend vertically downward from the installation holes reserved for the bottom plate 340 of the thermal insulation tank and the bottom plate 218 of the rocking plate.
  • the tank cover 402 and the flange of the outer tank 414 are sealed and connected through the outer tank body flange sealing rubber ring 423 ; the tank cover 402 is provided with several air filters 403 .
  • the inner tank 405 is inserted inside the outer tank 414 , and the bottom of the inner tank 405 is provided with a positioning seat, and the positioning seat is inserted and connected to the positioning post 425 at the bottom of the outer tank 414 .
  • the fluid circulation pump includes: a movable bracket 600; the movable bracket 600 includes: a bracket 601, a movable bracket bottom plate 610, and a movable bracket four-wheel 620; the top of the bracket 601 By being provided with a tube clip 605, the tube clip 605 is used for fitting the support shaft 220 of the downward rocker, and the shaker body 202 is installed on the support shaft 220 of the downward rocker; the lower part of the bracket 601 is provided with There is a movable support base plate 610 ; the bottom of the support 601 is provided with four movable support wheels 620 .
  • the shaker body 202 is mounted on the support shaft 220 of the drop-down shaker.
  • the rocking plate 208 on the top of the rocker body 202 is installed on the upper bearing plate 210; the four corner positions of the upper bearing plate 210 are respectively installed on the upper ends of the four downwardly probed columns 214, and the four downwardly probed columns
  • a column fixing frame 216 is installed in the middle of the 214; the lower ends of the four downwardly probed columns 214 are respectively installed on the rocking plate bottom plate 218;
  • the sleeve locking screw 322 is installed on the outside of the center line of the sliding sleeve 320; the sliding sleeve 320 is slidably installed with a heat preservation tank body that can be opened and closed, and a space between the bottom of the heat preservation tank body and the bottom plate 218 of the rocking plate is reserved.
  • the installation port extending vertically downward for the pipeline meets the fluid mechanics requirements of the circulating pump, which is better than the existing traditional shaking table. Because the traditional shaker is provided with the shaker body (the part of the shaker drive box) at the lower part of the shaker, due to structural limitations, there is no space for the pipeline to protrude vertically downward in the middle of the shaker, and the pipeline must be bent and arranged so that the The fluid mechanics angle is obviously not as good as the down-type shaking table in this embodiment.
  • the specific form of the shaker body 202 is not limited, and reference may be made to the prior art.
  • the shaker body 202 includes: a shaker drive box; a drive motor is installed in the shaker drive box; a small pulley is installed on the power output shaft of the drive motor; the small pulley and the large pulley are connected by belt tensioning;
  • the large pulley is installed on the active eccentric shaft; the upper end of the active eccentric shaft is connected to the upper swing plate; the upper swing plate is connected to four sets of driven shafts; the upper swing plate is connected to the swing plate 208 by bolts, and the swing plate 208 is mounted on the upper bearing plate 210 .
  • the upper bearing plate 210 is fixed on the rocking plate 208 , and four descending columns 214 are installed downwardly under the upper bearing plate 210 , and the lower end of the descending columns 214 is equipped with a rocking plate bottom plate. 218.
  • a column fixing frame 216 is installed on the upper half of the four columns to ensure the rigidity and stability of the frame; a sliding sleeve 320, a sleeve locking screw 322 and a stopper 312 are installed on the bottom plate 218 of the rocking plate, and the two sliding sleeves 320 are installed on top
  • the bottom plate 340 of the thermal insulation tank is mounted on the thermal insulation tank which can be divided into two halves, and the installation of the equipment is completed.
  • the openable and closable thermal insulation tank includes: a bottom plate 340 of the thermal insulation tank, a front half of the thermal insulation tank 301 and a rear half of the thermal insulation tank 300; the bottom 340 of the thermal insulation tank is installed with the front half of the thermal insulation tank body 301 and the rear half body 300 of the insulation tank; the bottom of the insulation tank bottom plate 340 is provided with a sliding seat 321 for fitting on the sliding sleeve 320; the front half body 301 of the insulation tank and the rear half body 300 of the insulation tank
  • the rotating side is connected by the heat preservation tank body hinge 330; the front half body 301 of the heat preservation tank and the rear half body 300 of the heat preservation tank are provided with locking bolts 350 on the opening and closing side.
  • the bottom plate 340 of the thermal insulation tank body is provided with a U-shaped installation port.
  • the bottom plate 218 of the rocking plate is also provided with a U-shaped installation opening.
  • a space for accommodating the double-layer hard plastic shaker 400 is formed between the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank.
  • the maximum opening and closing angle between the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank can be set to 79°.
  • the bottom plate 218 of the rocking plate is provided with a stopper 312 on the sliding path of the thermal insulation tank, and the outer side of the bottom plate 340 of the thermal insulation tank has an L-shaped engaging portion;
  • the L-shaped latching portion on the outer side of the bottom plate 340 of the thermal insulation tank body is adapted to fit.
  • tank positioning pins 303 are arranged between the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank.
  • the cell mixture flows in one direction in the large circulation loop inside the stirring tank and inside and outside the double-layer hard plastic shaking tank, the flow rate is stable, there is no frequency, and the direction and pressure repeatedly change at high speed.
  • Cell damage is very small (because animal cells themselves have no cell wall, only a thin cell membrane, which can be broken by a small shear force).
  • the volume of the shaking tank can be made large, the diameter of the circulation pipeline can also be made large, and the shaking speed can also be made large.
  • the flow rate in the large circulation loop can reach It is very large, and the flow rate can also reach very high.
  • the volume of the shaker is 20 liters
  • the rotation speed is 80 revolutions per minute
  • the flow measurement is 4 times the volume, that is, 80 liters per minute.
  • the volume of the shaking tank of the present invention can be enlarged to 200 liters or even 500 liters, which far exceeds the flow rate of the existing cell trapping devices in the world. In this way, the larger the circulating flow rate, the higher the dissolved oxygen level and the faster the dissolved oxygen speed.
  • the present invention can better satisfy the large-volume and high-density large-scale animal cell culture.
  • the third embodiment provides a large-circulation cell retention device based on the above-mentioned first and second embodiments, including: a supernatant extraction and backwashing system and the fluid circulation described in the second embodiment Pump.
  • the large-circulation cell retention device specifically includes: a descending shaker, a double-layer hard plastic shaker 400, a stirring tank 102, a movable support 600, and a supernatant extraction and backwashing system;
  • the supernatant extraction and backwashing system includes: a hollow fiber microfiltration membrane column 500, a peristaltic pump 570, a diaphragm pump assembly 560, a heat preservation tank 586, a supernatant Liquid turnover bag 580, supernatant liquid storage bag 583 and supernatant liquid storage tank 585; the upper part of the hollow fiber microfiltration membrane column 500 has a supernatant liquid extraction outlet 520, and the lower part of the hollow fiber microfiltration membrane column 500 has supernatant liquid
  • the upper part is connected, and the lower part of the supernatant liquid turnover bag 580 is connected with the diaphragm pump assembly 560; the middle part of the supernatant liquid turnover bag 580 is connected with the supernatant liquid storage bag 583 in the supernatant liquid storage tank 585;
  • the diaphragm pump assembly 560 is connected to the supernatant backwash inlet 510 .
  • the working process of the supernatant extraction and backwashing system is as follows: the upper end of the hollow fiber microfiltration membrane column 500 is connected to the water outlet on the upper part of the stirring tank 102 through the liquid inlet silicone hose 503, and the cell mixture flows into the hollow fiber from top to bottom.
  • the microfiltration membrane column 500 flows out to the lower end, and flows out through the liquid outlet silicone hose 504 connected to the lower part of the stirring tank 102 (the liquid outlet silicone hose 504 is fixed by the silicone tube strap 507 ).
  • the hollow fiber microfiltration membrane column 500 has a supernatant extraction outlet 520 in the upper part, and a supernatant backwash inlet 510 in the lower part; the hollow fiber microfiltration membrane column 500 has a hollow fiber membrane 502 .
  • the hollow fiber microfiltration membrane column 500 is fixed on the outer wall of the stirring tank 102 by the fixing clip 590; after the peristaltic pump 570 draws out the supernatant through the peristaltic pump hose 572, it is then pumped into the supernatant turnover bag 580; the supernatant turnover
  • the bag 580 has an air filter 582 in the upper part and a supernatant overflow port in the middle. When the supernatant liquid level is higher than the supernatant liquid overflow port, the supernatant liquid will flow into the supernatant liquid storage bag 583 from the supernatant liquid inlet 589 for storage.
  • the supernatant liquid storage bag 583 has an air filter 587 above.
  • the lower part of the supernatant turnover bag 580 has a liquid outlet, which is used for backwashing.
  • the supernatant liquid turnover bag 580 is entirely housed in the thermal insulation tank body; the supernatant liquid storage bag 593 is specially used for storing the supernatant liquid overflowing from the supernatant liquid overflow port of the supernatant liquid turnover bag 580, and it is also used for storing the supernatant liquid. 10 in a sealed sterile state.
  • the diaphragm pump assembly 570 is connected to the supernatant backflush inlet 510 at the outer lower part of the hollow fiber microfiltration membrane column through a silicone hose at the front end, and is connected to the upper part through a silicone hose at the rear end.
  • the outflow port of the clear liquid turnover bag 580, the diaphragm pump assembly 570 is provided with a front one-way check valve 564 and a rear one-way check valve 562; at the same time, the silicone hollow ball with rebound vacuum capability and the up and down reciprocating pressure to open electromagnet assembly.
  • the fluid circulation pump includes: a double-layer hard plastic shaking tank 400, a stirring tank 102, and the downward-penetrating shaking table 200 described in the first embodiment.
  • the double-layer hard plastic shaker 400 is set in a heat-insulating tank body that can be opened and closed;
  • the water return ports 420 are connected by two return water silicone hoses 421;
  • the water outlet 410 at the bottom of the outer tank 414 of the double-layer hard plastic shaker 400 passes through the water outlet at the bottom of the mixing tank 102 and the bottom of the outer tank 414.
  • Silicone hose 411 is connected. It is explained that the static liquid level of the fluid circulation pump is located above the upper water outlet of the stirring tank and below the water outlet of the inner tank.
  • the fluid circulation pump uses a downward-penetrating shaker as the motive force to shake the double-layer rigid plastic shaker clockwise (450 degrees in the clockwise direction), and is connected to the stirring tank, so that the mixed culture fluid circulates in the shaking tank, the stirring tank and the pipeline; the The fluid circulation pump is mounted on the movable bracket through the support shaft of the descending shaker.
  • a stirring shaft 108 is provided in the stirring tank 102 , a stirring paddle 120 is installed on the stirring shaft 108 , and a motor 110 is installed on the end of the stirring shaft 108 .
  • any one of the water outlet silica gel hose 411 and the two return water silica gel hoses 421 is provided with a hollow fiber microfiltration membrane column 500; the hollow fiber microfiltration membrane column 500 is connected to the stirring through a fixing clip Tank 102 is connected.
  • the double-layer hard plastic shaker 400 includes: an outer tank 414, an inner tank 405 and a tank cover 402; the bottom center of the outer tank 414 is provided with an outer tank bottom water outlet 410; The upper part of the outer tank 414 is in the shape of a conical tank, and the lower part of the outer tank 414 is in the shape of a drum tank; the outer tank 414 is symmetrically provided with two water inlet protrusions 422 at the position of the upper conical tank; The bottom of the outer tank 414 is provided with four positioning posts 425; the outer tank bottom water outlet 410 at the bottom of the outer tank 414 can be perpendicular to the mounting holes reserved for the bottom plate 340 of the thermal insulation tank and the bottom plate 218 of the rocking plate.
  • the bottom of the inner tank 405 is symmetrically provided with two water return ports 420; the upper part of the inner tank 405 is in the shape of a conical tank, and the lower part of the inner tank 405 is in the shape of a drum;
  • the tank 405 is provided with an inner tank water outlet symmetrically at the position of the upper conical tank body; one side edge of the inner tank water outlet is provided with an inner tank water outlet tangential flow baffle 461; the bottom side edge of the inner tank water outlet A horizontal flow baffle 462 at the lower part of the water outlet of the inner tank is provided; the two water return ports 420 at the bottom of the inner tank 405 can extend vertically downward from the installation holes reserved for the bottom plate 340 of the thermal insulation tank and the bottom plate 218 of the rocking plate.
  • the tank cover 402 and the flange of the outer tank 414 are sealed and connected through the outer tank body flange sealing rubber ring 423 ; the tank cover 402 is provided with several air filters 403 .
  • the inner tank 405 is inserted inside the outer tank 414 , and the bottom of the inner tank 405 is provided with a positioning seat, and the positioning seat is inserted and connected to the positioning post 425 at the bottom of the outer tank 414 .
  • the fluid circulation pump includes: a movable bracket 600; the movable bracket 600 includes: a bracket 601, a movable bracket bottom plate 610, and a movable bracket four-wheel 620; the top of the bracket 601 By being provided with a tube clip 605, the tube clip 605 is used for fitting the support shaft 220 of the downward rocker, and the shaker body 202 is installed on the support shaft 220 of the downward rocker; the lower part of the bracket 601 is provided with There is a movable support base plate 610 ; the bottom of the support 601 is provided with four movable support wheels 620 .
  • the shaker body 202 is mounted on the support shaft 220 of the drop-down shaker.
  • the rocking plate 208 on the top of the rocker body 202 is installed on the upper bearing plate 210; the four corner positions of the upper bearing plate 210 are respectively installed on the upper ends of the four downwardly probed columns 214, and the four downwardly probed columns
  • a column fixing frame 216 is installed in the middle of the 214; the lower ends of the four downwardly probed columns 214 are respectively installed on the rocking plate bottom plate 218;
  • the sleeve locking screw 322 is installed on the outside of the center line of the sliding sleeve 320; the sliding sleeve 320 is slidably installed with a heat preservation tank body that can be opened and closed, and a space between the bottom of the heat preservation tank body and the bottom plate 218 of the rocking plate is reserved.
  • the installation port extending vertically downward for the pipeline meets the fluid mechanics requirements of the circulating pump, which is better than the existing traditional shaking table. Because the traditional shaker is provided with the shaker body (the part of the shaker drive box) at the lower part of the shaker, due to structural limitations, there is no space for the pipeline to protrude vertically downward in the middle of the shaker, and the pipeline must be bent and arranged so that the The fluid mechanics angle is obviously not as good as the down-type shaking table in this embodiment.
  • the specific form of the shaker body 202 is not limited, and reference may be made to the prior art.
  • the shaker body 202 includes: a shaker drive box; a drive motor is installed in the shaker drive box; a small pulley is installed on the power output shaft of the drive motor; the small pulley and the large pulley are connected by belt tensioning;
  • the large pulley is installed on the active eccentric shaft; the upper end of the active eccentric shaft is connected to the upper swing plate; the upper swing plate is connected to four sets of driven shafts; the upper swing plate is connected to the swing plate 208 by bolts, and the swing plate 208 is mounted on the upper bearing plate 210 .
  • the upper bearing plate 210 is fixed on the rocking plate 208 , and four descending columns 214 are installed downwardly under the upper bearing plate 210 , and the lower end of the descending columns 214 is equipped with a rocking plate bottom plate. 218.
  • a column fixing frame 216 is installed on the upper half of the four columns to ensure the rigidity and stability of the frame; a sliding sleeve 320, a sleeve locking screw 322 and a stopper 312 are installed on the bottom plate 218 of the rocking plate, and the two sliding sleeves 320 are installed on top
  • the bottom plate 340 of the thermal insulation tank is mounted on the thermal insulation tank which can be divided into two halves, and the installation of the equipment is completed.
  • the openable and closable thermal insulation tank includes: a bottom plate 340 of the thermal insulation tank, a front half of the thermal insulation tank 301 and a rear half of the thermal insulation tank 300; the bottom 340 of the thermal insulation tank is installed with the front half of the thermal insulation tank body 301 and the rear half body 300 of the insulation tank; the bottom of the insulation tank bottom plate 340 is provided with a sliding seat 321 for fitting on the sliding sleeve 320; the front half body 301 of the insulation tank and the rear half body 300 of the insulation tank
  • the rotating side is connected by the heat preservation tank body hinge 330; the front half body 301 of the heat preservation tank and the rear half body 300 of the heat preservation tank are provided with locking bolts 350 on the opening and closing side.
  • the bottom plate 340 of the thermal insulation tank body is provided with a U-shaped installation port.
  • the bottom plate 218 of the rocking plate is also provided with a U-shaped installation opening.
  • a space for accommodating the double-layer hard plastic shaker 400 is formed between the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank.
  • the maximum opening and closing angle between the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank can be set to 79°.
  • the bottom plate 218 of the rocking plate is provided with a stopper 312 on the sliding path of the thermal insulation tank, and the outer side of the bottom plate 340 of the thermal insulation tank has an L-shaped engaging portion;
  • the L-shaped latching portion on the outer side of the bottom plate 340 of the thermal insulation tank body is adapted to fit.
  • tank positioning pins 303 are arranged between the front half body 301 of the thermal insulation tank and the rear half body 300 of the thermal insulation tank.
  • the cell mixture flows in one direction in the large circulation loop inside the stirring tank and inside and outside the double-layer hard plastic shaking tank, the flow rate is stable, there is no frequency, and the direction and pressure repeatedly change at high speed.
  • Cell damage is very small (because animal cells themselves have no cell wall, only a thin cell membrane, which can be broken by a small shear force).
  • the cell concentration of the cell mixture is always the same as the cell concentration of the cell mixture in the stirring tank, the supernatant does not increase the concentration when the supernatant is extracted, and the extraction is easy .
  • the volume of the shaking tank can be increased, the diameter of the circulation pipeline can also be increased, and the shaking speed can also be increased.
  • the flow rate can also be very high.
  • the volume of the shaker is 20 liters
  • the rotation speed is 80 revolutions per minute
  • the flow measurement is 4 times the volume, that is, 80 liters per minute.
  • the volume of the shaking tank of the present invention can be enlarged to 200 liters or even 500 liters, which far exceeds the flow rate of the existing cell trapping devices in the world. In this way, the larger the circulating flow rate, the higher the dissolved oxygen level and the faster the dissolved oxygen speed.
  • the present invention can better satisfy the large-volume and high-density large-scale animal cell culture.

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Abstract

本发明提供一种大循环细胞截留装置、流体循环泵以及下探式摇床。本发明属于细胞截留装置技术领域。该下探式摇床包括：摇床本体；该摇床本体顶部的摇盘安装于上承重板上；该上承重板的四个边角位置分别安装于四个下探立柱的上端，该四个下探立柱的中部安装有立柱固定框；该四个下探立柱的下端分别安装在摇盘底板上；该摇盘底板安装有滑动套管和套管锁定螺钉，该套管锁定螺钉安装在滑动套管的中心线外侧；该滑动套管滑动安装有可开合的保温罐体。该流体循环泵包括：双层硬塑摇罐、搅拌罐以及该下探式摇床。该大循环细胞截留装置包括：上清液抽取与反冲洗***以及该流体循环泵。

Description

一种大循环细胞截留装置、流体循环泵以及下探式摇床 技术领域
本发明涉及细胞截留装置技术领域，尤其是涉及一种大循环细胞截留装置、流体循环泵以及下探式摇床。
背景技术
当前，世界生物技术制药产业发展迅猛，并已取得了巨大的成就。通过动物细胞体外培养表达和生产各类诊断和治疗用单克隆抗体、疫苗、生长因子等生物活性蛋白具有十分广泛的市场应用前景。由于采用灌流工艺大规模悬浮培养动物细胞时具有高质量高效益等优势，所以灌流工艺中的关键装备—细胞截留装置就成了最重要的生物工艺装备。因为没有该装备就不能实现灌流工艺，而且细胞截留装置的高效益很大程度上决定了生物技术制药企业的生产规模，产品成本和整体效益。
现在，世界上使用最多的主流细胞截留装置，除了都使用中空纤维切向流过滤技术外，均采用隔膜泵特有的“一抽一推”往复运动来使细胞混合液往复流动，在细胞混合液往复流动过程中，通过在中空纤维膜管外腔内使用蠕动泵抽出上清液，实现了灌流工艺培养细胞的关键步骤—在抽出上清液同时把细胞截留在反应罐中。由于中空纤维膜结构上的特点，以上这种方式能把细胞100％的截留在反应罐中，也正是这种隔膜泵造成细胞混合液在高频率地变换方向(一个往复两秒)还在同频率下变换液体压力，给细胞造成损伤。
另外，在这样流动的环境下，一方面因细胞混合液流动的方向是和中空纤维管的中心线是平行的，抽入和推出细胞混合液时都平行于中空纤维管的中心线，只是一进一出流动方向是相反的。当蠕动泵抽出上清液时，造成中空纤维管外腔的区域呈负压，使得在中空纤维膜管内流动的细胞混合液中的部分细胞因中空纤维膜管外腔的负压作用也与上清液一起向管外流动，当细胞到达中空纤维膜管内壁的微孔时有少量细胞就堵在了这个微孔上，而没有被管内向下流动的混合液带着一同流下去。这样，时间一长造成积累，逐渐的中空纤维膜管内壁上的微孔大部分被细胞堵住。就抽不 出上清液来，造成细胞截留装置失效。要继续进行灌流工艺培养必须要再换一个新装置，由于该装置价格不菲，会造成成本的大大增加。
公开于该背景技术部分的信息仅仅旨在加深对本发明的总体背景技术的理解，而不应当被视为承认或以任何形式暗示该信息构成已为本领域技术人员所公知的现有技术。
发明内容
本发明的目的在于提供一种大循环细胞截留装置、流体循环泵以及下探式摇床，以解决现有技术中存在的技术问题。
为了实现上述目的，本发明采用以下技术方案：
第一方面，本发明一种下探式摇床，其包括：摇床本体；
所述摇床本体顶部的摇盘安装于上承重板上；所述上承重板的四个边角位置分别安装于四个下探立柱的上端，所述四个下探立柱的中部安装有立柱固定框；所述四个下探立柱的下端分别安装在摇盘底板上；所述摇盘底板安装有滑动套管和套管锁定螺钉，所述套管锁定螺钉安装在滑动套管的中心线外侧；所述滑动套管上部安装有保温罐体底板与可开合的保温罐体，所述保温罐体的底部与摇盘底板上都预留有供管路垂直向下伸出的安装口。
作为一种进一步的技术方案，所述可开合的保温罐体包括：保温罐体底板、保温罐前半体和保温罐后半体；所述保温罐体底板安装有保温罐前半体和保温罐后半体；所述保温罐体底板的底部设置有用于套装在所述滑动套管上的滑座；所述保温罐前半体与保温罐后半体在转动侧通过保温罐体折页连接；所述保温罐前半体与保温罐后半体在开合侧设置有锁紧螺栓。
作为一种进一步的技术方案，所述摇盘底板在保温罐体的滑动路径上设置有挡块，所述保温罐体底板的外侧具有L型卡抵部；所述挡块与所述保温罐体底板外侧的L型卡抵部相适配。
作为一种进一步的技术方案，所述保温罐前半体和保温罐后半体之间设置有四个罐用定位销，所述四个罐用定位销既有前后半体合体定位作用同时还能使保温罐前后半体合体后共同承重。
采用上述技术方案，本发明具有如下有益效果：
本发明中的下探式摇床可满足循环泵的流体力学要求，相比于现有传统的摇床而言效果更好。因为传统的摇床在其下部设置摇床本体(摇床驱动机构部分)，由于结构限制，在摇床的中间位置没有供管路垂直向下伸出 的空间，管路要拐弯设置，这样从流体力学的角度，显然不如本实施例中的下探式摇床效果好。
第二方面，本发明提供一种流体循环泵，其包括：双层硬塑摇罐、搅拌罐以及上述的下探式摇床；所述双层硬塑摇罐设置于可开合的保温罐体中；所述搅拌罐的上部出水口与所述双层硬塑摇罐的内罐底部的两回水口之间通过两回水硅胶软管连接；所述搅拌罐的下部进水口与所述双层硬塑摇罐的外罐底部的外罐底出水口之间通过出水硅胶软管连接；所述搅拌罐内设置有搅拌轴，所述搅拌轴安装搅拌桨，所述搅拌轴的端部安装有电机。
作为一种进一步的技术方案，所述双层硬塑摇罐包括：外罐、内罐和罐盖；所述外罐的底部中心位置设置有外罐底出水口；所述外罐的上部呈圆锥罐体状，所述外罐的下部呈圆桶罐体状；所述外罐在其上部圆锥罐***置对称设置有两个进水凸部；所述外罐的底部设置有四个定位柱；所述外罐底部的外罐底出水口能从所述保温罐体底板、所述摇盘底板预留的安装孔中垂直向下伸出；所述内罐的底部对称设置有两回水口；所述内罐的上部呈圆锥罐体状，所述内罐的下部呈圆桶罐体状；所述内罐在其上部圆锥罐***置对称设置有内罐出水口；所述内罐出水口的一侧边缘设置有内罐出水口切向流挡板；所述内罐出水口的底侧边缘设置有内罐出水口下部水平流挡板；所述内罐底部的两回水口能从所述保温罐体底板、所述摇盘底板预留的安装孔中垂直向下伸出；所述罐盖与所述外罐的法兰之间通过外罐体法兰密封胶圈密封连接；所述罐盖上设置有若干个空气过滤器。
作为一种进一步的技术方案，所述内罐插装于所述外罐的内部，且所述内罐的底部设置有定位座，所述定位座与所述外罐底部定位柱插装连接。
作为一种进一步的技术方案，所述出水硅胶软管和两回水硅胶软管之中的任意一者设置有中空纤维微滤膜柱；所述中空纤维微滤膜柱通过固定夹与所述搅拌罐连接。
作为一种进一步的技术方案，该流体循环泵包括：可移动支架；所述可移动支架包括：支架、可移动支架底板、可移动支架四走轮；所述支架的顶部通过设置有管卡，所述管卡用于穿装下探式摇床支撑轴，所述摇床本体安装于下探式摇床支撑轴上；所述支架的下部设置有可移动支架底板；所述支架的底部设置有可移动支架四走轮。
采用上述技术方案，本发明具有如下有益效果：
本发明中的流体循环泵在细胞截留过程中，细胞混合液是单方向在搅拌罐内和双层硬塑摇罐内外的大循环回路中流动，流速稳定，无频率，方 向与压力的高速反复变化，细胞损伤非常小(因动物细胞本身无细胞壁，只有薄薄的细胞膜,很小的剪切力就可弄破这细胞膜从而导致细胞死亡)。而且，在细胞截留过程中，因双层硬塑摇罐内混合液的振荡运动，扬起水花与水珠的作用，大大增加了摇罐中的气液相比表面积，从而就大大增加了溶氧水平和速度，同时也大大提高了排除混合液中的二氧化碳，氨气等有害气体的速度，具有增氧与排出有害气体的净化功能。目前，世界上现有细胞截留装置还不具备这两项功能。
第三方面，本发明还提供一种大循环细胞截留装置，其包括：上清液抽取与反冲洗***以及上述的流体循环泵；所述上清液抽取与反冲洗***包括：中空纤维微滤膜柱、蠕动泵、隔膜泵总成、保温罐、上清液周转袋、上清液存储袋和上清液存储罐；所述中空纤维微滤膜柱上部有上清液抽出口，所述中空纤维微滤膜柱下部有上清液反冲洗入口；所述蠕动泵的蠕动泵软管的一端与上清液抽出口连接，所述蠕动泵的蠕动泵软管的另一端与上清液周转袋的上部连接，所述上清液周转袋的下部与隔膜泵总成连接；所述上清液周转袋的中部与上清液存储罐内的上清液存储袋连接；所述隔膜泵总成与上清液反冲洗入口连接。
采用上述技术方案，本发明具有如下有益效果：
本发明在细胞截留过程中，细胞混合液是单方向在搅拌罐内和双层硬塑摇罐内外的大循环回路中流动，流速稳定，无频率，方向与压力的高速反复变化，细胞损伤非常小(因动物细胞本身无细胞壁，只有薄薄的细胞膜,很小的剪切力就可弄破这细胞膜造成细胞死亡)。
本发明的大循环细胞截留装置在抽取的上清液时，细胞混合液的细胞浓度始终是和搅拌罐里的细胞混合液的细胞浓度是一样的，抽取上清液不增加浓度，抽取很容易。
本发明的大循环细胞截留装置的反冲洗***冲洗堵在中空纤维膜管壁微孔上的细胞时，每次都能冲洗干净，无残留。没有长时间积累的问题。原因是反冲洗是在中空纤维膜管微孔的外法线方向，从中空纤维膜管外向管内加压冲洗。这样冲力方向准确很容易冲洗掉所有堵在微孔上的细胞，与在中空纤维膜管内的从上向下流的细胞混合液一起流出中空纤维微滤膜柱的下端。而且只用很少的反冲洗液，极短暂的冲洗时间，这是本发明中反冲洗***的特殊优势。
本发明在细胞截留过程中，因罐内混合液的振荡运动，扬起水花与水珠的作用，大大增加了摇罐中的气液相比表面积，从而就大大增加了溶氧 水平和速度，同时也大大提高了排除混合液中的二氧化碳，氨气等有害气体的速度，具有增氧与排出有害气体的净化功能。目前，世界上现有细胞截留装置还不具备这两项功能。
本发明由于摇罐的容积可放得很大，循环管路的管径也可放得很大，摇动速度也可放得很大，其结果就是大循环的回路中的流量能达很大，流速也能达到很高。例如：摇罐的容积是20升，转速为每分钟80转，流量测量是4倍容积，即80升每分钟。而且本发明的摇罐容积可放大到200升甚至放大到500升，远远超过世界上现有的细胞截留装置的流量。这样循环流量越大，溶氧水平就越高，溶氧速度也越快，本发明能更好地满足大容积，高密度的大规模动物细胞培养。
附图说明
为了更清楚地说明本发明具体实施方式或现有技术中的技术方案，下面将对具体实施方式或现有技术描述中所需要使用的附图作简单的介绍，显而易见地，下面描述中的附图是本发明的一些实施方式，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为本发明实施例一提供的下探式摇床的侧视图；
图2为本发明实施例一提供的下探式摇床的俯视图；
图3为本发明实施例一提供的下探式摇床原位状态的俯视图；
图4为本发明实施例一提供的下探式摇床拉出保温罐体状态的俯视图；
图5为本发明实施例一提供的下探式摇床打开保温罐体且装入双层硬塑摇罐状态的俯视图；
图6为本发明实施例一提供的下探式摇床合上保温罐体，推回保温罐体并锁紧在工作位状态的俯视图；
图7为本发明实施例一提供的流体循环泵的侧视图；
图8为本发明实施例一提供的双层硬塑摇罐的侧视图；
图9为本发明实施例一提供的双层硬塑摇罐的俯视图；
图10为本发明实施例一提供的可移动支架的侧视图；
图11为本发明实施例一提供的可移动支架的俯视图；
图12为本发明实施例一提供的大循环细胞截留装置的侧视图；
图13为本发明实施例一提供的上清液抽取与反冲洗***的侧视图。
具体实施方式
下面将结合附图对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
以下结合附图对本发明的具体实施方式进行详细说明。应当理解的是，此处所描述的具体实施方式仅用于说明和解释本发明，并不用于限制本发明。
实施例一
结合图1、图2所示，本实施例一提供一种下探式摇床，其包括：摇床本体202；所述摇床本体202安装于下探式摇床支撑轴220上。所述摇床本体202顶部的摇盘208安装于上承重板210上；所述上承重板210的四个边角位置分别安装于四个下探立柱214的上端，所述四个下探立柱214的中部安装有立柱固定框216；所述四个下探立柱214的下端分别安装在摇盘底板218上；所述摇盘底板218安装有滑动套管320和套管锁定螺钉322，所述套管锁定螺钉322安装在滑动套管320的中心线外侧；所述滑动套管320滑动安装有可开合的保温罐体，所述保温罐体的底部与摇盘底板218之间预留有供管路垂直向下伸出的安装口，满足循环泵的流体力学要求，相比于现有传统的摇床而言效果更好。因为传统的摇床在其下部设置摇床本体(摇床驱动箱部分)，由于结构限制，在摇床的中间位置没有供管路垂直向下伸出的空间，管路要拐弯设置，这样从流体力学的角度，显然不如本实施例中的下探式摇床效果好。
本实施例中，摇床本体202的具体形式并不局限，可参照现有技术。
例如：摇床本体202包括：摇床驱动箱(偏心安装，以图示偏心距206为参照)；摇床驱动箱内安装有驱动电机；所述驱动电机的动力输出轴安装小皮带轮；所述小皮带轮与大皮带轮之间通过皮带张紧连接；所述大皮带轮安装于主动偏心轴上；所述主动偏轴的上端连接上摇动盘；所述上摇动盘连接四组从动轴；所述上摇动盘通过螺栓连接于摇盘208，摇盘208安装于上承重板210上。可见，本实施例中的下探式摇床，在摇盘208上固定上承重板210，在上承重板210下面向下装四个下探立柱214，该下探立柱214下端装摇盘底板218。四立柱上半部装一个立柱固定框216，来保证框的刚性与稳定性；在摇盘底板218上面安装滑动套管320和套管锁定螺钉322及挡块312，两滑动套管320顶上装保温罐体底板340，其上再装上可 分成两半的保温罐体，至此设备安装完毕。
结合图1至图6所示，本实施例中，优选地，所述可开合的保温罐体包括：保温罐体底板340、保温罐前半体301和保温罐后半体300；所述保温罐体底板340安装有保温罐前半体301和保温罐后半体300；所述保温罐体底板340的底部设置有用于套装在所述滑动套管320上的滑座321；所述保温罐前半体301与保温罐后半体300在转动侧通过保温罐体折页330连接；所述保温罐前半体301与保温罐后半体300在开合侧设置有锁紧螺栓350。
本实施例中，优选地，保温罐体底板340设置有U型的安装口。
对应地，摇盘底板218也设置有U型的安装口。
同时，保温罐前半体301和保温罐后半体300之间形成可容纳双层硬塑摇罐400的空间。保温罐前半体301和保温罐后半体300之间的最大开合角度可设置79°。
本实施例中，优选地，所述摇盘底板218在保温罐体的滑动路径上设置有挡块312，所述保温罐体底板340的外侧具有L型卡抵部；所述挡块312与所述保温罐体底板340外侧的L型卡抵部相适配。
本实施例中，优选地，所述保温罐前半体301和保温罐后半体300之间设置有四个罐用定位销303。
实施例二
本实施例二在上述实施例一的基础上提供一种流体循环泵。
结合图7至图11所示，该流体循环泵包括：双层硬塑摇罐400、搅拌罐102以及实施例一所述的下探式摇床200。
本实施例中，所述双层硬塑摇罐400设置于可开合的保温罐体中；所述搅拌罐的上部出水口与所述双层硬塑摇罐400的内罐405底部的两回水口420之间通过两回水硅胶软管421连接；所述搅拌罐102的下部进水口与所述双层硬塑摇罐400的外罐414底部的外罐底出水口410之间通过出水硅胶软管411连接。说明的是，该流体循环泵的静态液面处于所述搅拌罐的上部出水口之上且位于内罐出水口之下的位置。该流体循环泵使用下探式摇床为原动力顺时针摇动双层硬塑摇罐(顺时针方向450)，连接搅拌罐，使混合培养液在摇罐与搅拌罐及管路内循环流动；该流体循环泵是通过下探式摇床支撑轴安装在可移动支架上。
本实施例中，优选地，所述搅拌罐102内设置有搅拌轴108，所述搅拌轴108安装搅拌桨120，所述搅拌轴108的端部安装有电机110。优选地， 所述出水硅胶软管411和两回水硅胶软管421之中的任意一者设置有中空纤维微滤膜柱500；所述中空纤维微滤膜柱500通过固定夹与所述搅拌罐102连接。
本实施例中，优选地，所述双层硬塑摇罐400包括：外罐414、内罐405和罐盖402；所述外罐414的底部中心位置设置有外罐底出水口410；所述外罐414的上部呈圆锥罐体状，所述外罐414的下部呈圆桶罐体状；所述外罐414在其上部圆锥罐***置对称设置有两个进水凸部422；所述外罐414的底部设置有四个定位柱425；所述外罐414底部的外罐底出水口410能从所述保温罐体底板340、所述摇盘底板218预留的安装孔中垂直向下伸出；所述内罐405的底部对称设置有两回水口420；所述内罐405的上部呈圆锥罐体状，所述内罐405的下部呈圆桶罐体状；所述内罐405在其上部圆锥罐***置对称设置有内罐出水口；所述内罐出水口的一侧边缘设置有内罐出水口切向流挡板461；所述内罐出水口的底侧边缘设置有内罐出水口下部水平流挡板462；所述内罐405底部的两回水口420能从所述保温罐体底板340、所述摇盘底板218预留的安装孔中垂直向下伸出；所述罐盖402与所述外罐414的法兰之间通过外罐体法兰密封胶圈423密封连接；所述罐盖402上设置有若干个空气过滤器403。
优选地，所述内罐405插装于所述外罐414的内部，且所述内罐405的底部设置有定位座，所述定位座与所述外罐414底部定位柱425插装连接。
本实施例中，优选地，该流体循环泵包括：可移动支架600；所述可移动支架600包括：支架601、可移动支架底板610、可移动支架四走轮620；所述支架601的顶部通过设置有管卡605，所述管卡605用于穿装下探式摇床支撑轴220，所述摇床本体202安装于下探式摇床支撑轴220上；所述支架601的下部设置有可移动支架底板610；所述支架601的底部设置有可移动支架四走轮620。
优选地，所述摇床本体202安装于下探式摇床支撑轴220上。所述摇床本体202顶部的摇盘208安装于上承重板210上；所述上承重板210的四个边角位置分别安装于四个下探立柱214的上端，所述四个下探立柱214的中部安装有立柱固定框216；所述四个下探立柱214的下端分别安装在摇盘底板218上；所述摇盘底板218安装有滑动套管320和套管锁定螺钉322，所述套管锁定螺钉322安装在滑动套管320的中心线外侧；所述滑动套管320滑动安装有可开合的保温罐体，所述保温罐体的底部与摇盘底板218之 间预留有供管路垂直向下伸出的安装口，满足循环泵的流体力学要求，相比于现有传统的摇床而言效果更好。因为传统的摇床在其下部设置摇床本体(摇床驱动箱部分)，由于结构限制，在摇床的中间位置没有供管路垂直向下伸出的空间，管路要拐弯设置，这样从流体力学的角度，显然不如本实施例中的下探式摇床效果好。
本实施例中，摇床本体202的具体形式并不局限，可参照现有技术。
例如：摇床本体202包括：摇床驱动箱；摇床驱动箱内安装有驱动电机；所述驱动电机的动力输出轴安装小皮带轮；所述小皮带轮与大皮带轮之间通过皮带张紧连接；所述大皮带轮安装于主动偏心轴上；所述主动偏轴的上端连接上摇动盘；所述上摇动盘连接四组从动轴；所述上摇动盘通过螺栓连接于摇盘208，摇盘208安装于上承重板210上。可见，本实施例中的下探式摇床，在摇盘208上固定上承重板210，在上承重板210下面向下装四个下探立柱214，该下探立柱214下端装摇盘底板218。四立柱上半部装一个立柱固定框216，来保证框的刚性与稳定性；在摇盘底板218上面安装滑动套管320和套管锁定螺钉322及挡块312，两滑动套管320顶上装保温罐体底板340，其上再装上可分成两半的保温罐体，至此设备安装完毕。
本实施例中，优选地，所述可开合的保温罐体包括：保温罐体底板340、保温罐前半体301和保温罐后半体300；所述保温罐体底板340安装有保温罐前半体301和保温罐后半体300；所述保温罐体底板340的底部设置有用于套装在所述滑动套管320上的滑座321；所述保温罐前半体301与保温罐后半体300在转动侧通过保温罐体折页330连接；所述保温罐前半体301与保温罐后半体300在开合侧设置有锁紧螺栓350。
本实施例中，优选地，保温罐体底板340设置有U型的安装口。
对应地，摇盘底板218也设置有U型的安装口。
同时，保温罐前半体301和保温罐后半体300之间形成可容纳双层硬塑摇罐400的空间。保温罐前半体301和保温罐后半体300之间的最大开合角度可设置79°。
本实施例中，优选地，所述摇盘底板218在保温罐体的滑动路径上设置有挡块312，所述保温罐体底板340的外侧具有L型卡抵部；所述挡块312与所述保温罐体底板340外侧的L型卡抵部相适配。
本实施例中，优选地，所述保温罐前半体301和保温罐后半体300之间设置有四个罐用定位销303。
本实施例中，在细胞截留过程中，细胞混合液是单方向在搅拌罐内和 双层硬塑摇罐内外的大循环回路中流动，流速稳定，无频率，方向与压力的高速反复变化，细胞损伤非常小(因动物细胞本身无细胞壁，只有薄薄的细胞膜,很小的剪切力就可弄破这细胞膜)。
本实施例中，在细胞截留过程中，因罐内混合液的振荡运动，扬起水花与水珠的作用，大大增加了摇罐中的气液相比表面积，从而就大大增加了溶氧水平和速度，同时也大大提高了排除混合液中的二氧化碳，氨气等有害气体的速度，具有增氧与排出有害气体的功能。目前，世界上现有细胞截留装置还不具备这两项功能。
本实施例中，由于摇罐的容积可放得很大，循环管路的管径也可放得很大，摇动速度也可放得很大，其结果就是大循环的回路中的流量能达很大，流速也能达到很高。例如：摇罐的容积是20升，转速为每分钟80转，流量测量是4倍容积，即80升每分钟。而且本发明的摇罐容积可放大到200升甚至放大到500升，远远超过世界上现有的细胞截留装置的流量。这样循环流量越大，溶氧水平就越高，溶氧速度也越快，本发明能更好地满足大容积，高密度的大规模动物细胞培养。
实施例三
结合图12所示，本实施例三在上述实施例一、实施例二的基础上提供一种大循环细胞截留装置，包括：上清液抽取与反冲洗***以及实施例二所述的流体循环泵。可以理解的是，该大循环细胞截留装置具体包括：下探式摇床、双层硬塑摇罐400、搅拌罐102、可移动支架600以及上清液抽取与反冲洗***；
如图13所示，本实施例中，优选地，所述上清液抽取与反冲洗***包括：中空纤维微滤膜柱500、蠕动泵570、隔膜泵总成560、保温罐586、上清液周转袋580、上清液存储袋583和上清液存储罐585；所述中空纤维微滤膜柱500上部有上清液抽出口520，所述中空纤维微滤膜柱500下部有上清液反冲洗入口510；所述蠕动泵570的蠕动泵软管572的一端与上清液抽出口520连接，所述蠕动泵570的蠕动泵软管572的另一端与上清液周转袋580的上部连接，所述上清液周转袋580的下部与隔膜泵总成560连接；所述上清液周转袋580的中部与上清液存储罐585内的上清液存储袋583连接；所述隔膜泵总成560与上清液反冲洗入口510连接。
所述上清液抽取与反冲洗***的工作过程为：中空纤维微滤膜柱500上端通过进液硅胶软管503与搅拌罐102上部的出水口连接，细胞混合液 从上向下流进中空纤维微滤膜柱500至下端流出，通过连接到搅拌罐102下部的出液口硅胶软管504流出(出液口硅胶软管504通过硅胶管绑带507固定)。中空纤维微滤膜柱500外上部有上清液抽出口520，下部有上清液反冲洗入口510；中空纤维微滤膜柱500具有中空纤维膜502。中空纤维微滤膜柱500被固定夹590固定在搅拌罐102外壁上；蠕动泵570通过蠕动泵软管572把上清液抽出后，再泵入上清液周转袋580中；上清液周转袋580上部有空气过滤器582，中部有上清液溢出口。当上清液面高于上清液溢出口时，上清液就会从上清液进口589流入上清液存储袋583存起来，上清液存储袋583的上方具有空气过滤器587。上清液周转袋580的下部有一出液口，是为反冲洗使用。上清液周转袋580整体都装在保温罐体中；所述上清液存储袋593是专门存储来自上清液周转袋580的上清液溢出口溢出的上清液用的，它也是处在密封无菌状态10。
本实施例中，优选地，所述隔膜泵总成570是通过前端的硅胶软管连接到中空纤维微滤膜柱外下部的上清液反冲入口510，通过后端的硅胶软管连接到上清液周转袋580的流出口，隔膜泵总成570带有前单向止回阀564、后单向止回阀562；同时，具有回弹真空能力的硅胶空球体和能上下往复压紧打开的电磁铁组件。
该流体循环泵包括：双层硬塑摇罐400、搅拌罐102以及实施例一所述的下探式摇床200。
本实施例中，所述双层硬塑摇罐400设置于可开合的保温罐体中；所述搅拌罐的上部出水口与所述双层硬塑摇罐400的内罐405底部的两回水口420之间通过两回水硅胶软管421连接；所述搅拌罐102的下部进水口与所述双层硬塑摇罐400的外罐414底部的外罐底出水口410之间通过出水硅胶软管411连接。说明的是，该流体循环泵的静态液面处于所述搅拌罐的上部出水口之上且位于内罐出水口之下的位置。该流体循环泵使用下探式摇床为原动力顺时针摇动双层硬塑摇罐(顺时针方向450)，连接搅拌罐，使混合培养液在摇罐与搅拌罐及管路内循环流动；该流体循环泵是通过下探式摇床支撑轴安装在可移动支架上。
本实施例中，优选地，所述搅拌罐102内设置有搅拌轴108，所述搅拌轴108安装搅拌桨120，所述搅拌轴108的端部安装有电机110。优选地，所述出水硅胶软管411和两回水硅胶软管421之中的任意一者设置有中空纤维微滤膜柱500；所述中空纤维微滤膜柱500通过固定夹与所述搅拌罐102连接。
本实施例中，优选地，所述双层硬塑摇罐400包括：外罐414、内罐405和罐盖402；所述外罐414的底部中心位置设置有外罐底出水口410；所述外罐414的上部呈圆锥罐体状，所述外罐414的下部呈圆桶罐体状；所述外罐414在其上部圆锥罐***置对称设置有两个进水凸部422；所述外罐414的底部设置有四个定位柱425；所述外罐414底部的外罐底出水口410能从所述保温罐体底板340、所述摇盘底板218预留的安装孔中垂直向下伸出；所述内罐405的底部对称设置有两回水口420；所述内罐405的上部呈圆锥罐体状，所述内罐405的下部呈圆桶罐体状；所述内罐405在其上部圆锥罐***置对称设置有内罐出水口；所述内罐出水口的一侧边缘设置有内罐出水口切向流挡板461；所述内罐出水口的底侧边缘设置有内罐出水口下部水平流挡板462；所述内罐405底部的两回水口420能从所述保温罐体底板340、所述摇盘底板218预留的安装孔中垂直向下伸出；所述罐盖402与所述外罐414的法兰之间通过外罐体法兰密封胶圈423密封连接；所述罐盖402上设置有若干个空气过滤器403。
优选地，所述内罐405插装于所述外罐414的内部，且所述内罐405的底部设置有定位座，所述定位座与所述外罐414底部定位柱425插装连接。
本实施例中，优选地，该流体循环泵包括：可移动支架600；所述可移动支架600包括：支架601、可移动支架底板610、可移动支架四走轮620；所述支架601的顶部通过设置有管卡605，所述管卡605用于穿装下探式摇床支撑轴220，所述摇床本体202安装于下探式摇床支撑轴220上；所述支架601的下部设置有可移动支架底板610；所述支架601的底部设置有可移动支架四走轮620。
优选地，所述摇床本体202安装于下探式摇床支撑轴220上。所述摇床本体202顶部的摇盘208安装于上承重板210上；所述上承重板210的四个边角位置分别安装于四个下探立柱214的上端，所述四个下探立柱214的中部安装有立柱固定框216；所述四个下探立柱214的下端分别安装在摇盘底板218上；所述摇盘底板218安装有滑动套管320和套管锁定螺钉322，所述套管锁定螺钉322安装在滑动套管320的中心线外侧；所述滑动套管320滑动安装有可开合的保温罐体，所述保温罐体的底部与摇盘底板218之间预留有供管路垂直向下伸出的安装口，满足循环泵的流体力学要求，相比于现有传统的摇床而言效果更好。因为传统的摇床在其下部设置摇床本体(摇床驱动箱部分)，由于结构限制，在摇床的中间位置没有供管路垂直 向下伸出的空间，管路要拐弯设置，这样从流体力学的角度，显然不如本实施例中的下探式摇床效果好。
本实施例中，摇床本体202的具体形式并不局限，可参照现有技术。
例如：摇床本体202包括：摇床驱动箱；摇床驱动箱内安装有驱动电机；所述驱动电机的动力输出轴安装小皮带轮；所述小皮带轮与大皮带轮之间通过皮带张紧连接；所述大皮带轮安装于主动偏心轴上；所述主动偏轴的上端连接上摇动盘；所述上摇动盘连接四组从动轴；所述上摇动盘通过螺栓连接于摇盘208，摇盘208安装于上承重板210上。可见，本实施例中的下探式摇床，在摇盘208上固定上承重板210，在上承重板210下面向下装四个下探立柱214，该下探立柱214下端装摇盘底板218。四立柱上半部装一个立柱固定框216，来保证框的刚性与稳定性；在摇盘底板218上面安装滑动套管320和套管锁定螺钉322及挡块312，两滑动套管320顶上装保温罐体底板340，其上再装上可分成两半的保温罐体，至此设备安装完毕。
本实施例中，优选地，所述可开合的保温罐体包括：保温罐体底板340、保温罐前半体301和保温罐后半体300；所述保温罐体底板340安装有保温罐前半体301和保温罐后半体300；所述保温罐体底板340的底部设置有用于套装在所述滑动套管320上的滑座321；所述保温罐前半体301与保温罐后半体300在转动侧通过保温罐体折页330连接；所述保温罐前半体301与保温罐后半体300在开合侧设置有锁紧螺栓350。
本实施例中，优选地，保温罐体底板340设置有U型的安装口。
对应地，摇盘底板218也设置有U型的安装口。
同时，保温罐前半体301和保温罐后半体300之间形成可容纳双层硬塑摇罐400的空间。保温罐前半体301和保温罐后半体300之间的最大开合角度可设置79°。
本实施例中，优选地，所述摇盘底板218在保温罐体的滑动路径上设置有挡块312，所述保温罐体底板340的外侧具有L型卡抵部；所述挡块312与所述保温罐体底板340外侧的L型卡抵部相适配。
本实施例中，优选地，所述保温罐前半体301和保温罐后半体300之间设置有四个罐用定位销303。
综上，本发明在细胞截留过程中，细胞混合液是单方向在搅拌罐内和双层硬塑摇罐内外的大循环回路中流动，流速稳定，无频率，方向与压力的高速反复变化，细胞损伤非常小(因动物细胞本身无细胞壁，只有薄薄的细胞膜,很小的剪切力就可弄破这细胞膜)。
本发明的大循环细胞截留装置在抽取的上清液时，细胞混合液的细胞浓度始终是和搅拌罐里的细胞混合液的细胞浓度是一样的，抽取上清液不增加浓度，抽取很容易。
本发明的大循环细胞截留装置的反冲洗***冲洗堵在中空纤维膜管微孔上的细胞时，每次都能冲洗干净，无残留。没有长时间积累的问题。原因是反冲洗是在中空纤维膜管微孔的外法线方向，从中空纤维膜管外向管内加压冲洗。这样冲力方向准确很容易冲洗掉全部堵在微孔上的细胞，与在中空纤维膜管内的从上向下流的细胞混合液一起流出中空纤维微滤膜柱的下端。而且只用很少的反冲洗液，极短暂的冲洗时间，这是本发明中反冲洗***的特殊优势。
本发明在细胞截留过程中，因罐内混合液的振荡运动，扬起水花与水珠的作用，大大增加了摇罐中的气液相比表面积，从而就大大增加了溶氧水平和速度，同时也大大提高了排除混合液中的二氧化碳，氨气等有害气体的速度，具有增氧与排出有害气体的功能。目前，世界上现有细胞截留装置还不具备这两项功能。
本发明由于摇罐的容积可放得很大，循环管路的管径也可放得很大，摇动速度也可放得很大，其结果就是大循环的回路中的流量能达很大，流速也能达到很高。例如：摇罐的容积是20升，转速为每分钟80转，流量测量是4倍容积，即80升每分钟。而且本发明的摇罐容积可放大到200升甚至放大到500升，远远超过世界上现有的细胞截留装置的流量。这样循环流量越大，溶氧水平就越高，溶氧速度也越快，本发明能更好地满足大容积，高密度的大规模动物细胞培养。
最后应说明的是：以上各实施例仅用以说明本发明的技术方案，而非对其限制；尽管参照前述各实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分或者全部技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。

Claims (10)

  1. 一种下探式摇床，其特征在于，包括：摇床本体(202)；
    所述摇床本体(202)顶部的摇盘(208)安装于上承重板(210)上；所述上承重板(210)的四个边角位置分别安装于四个下探立柱(214)的上端，所述四个下探立柱(214)的中部安装有立柱固定框(216)；所述四个下探立柱(214)的下端分别安装在摇盘底板(218)上；所述摇盘底板(218)安装有滑动套管(320)和套管锁定螺钉(322)，所述套管锁定螺钉(322)安装在滑动套管(320)的中心线外侧；所述滑动套管(320)滑动安装有可开合的保温罐体，所述保温罐体的底部与摇盘底板(218)之间预留有供管路垂直向下伸出的安装口。
  2. 根据权利要求1所述的下探式摇床，其特征在于，所述可开合的保温罐体包括：保温罐体底板(340)、保温罐前半体(301)和保温罐后半体(300)；所述保温罐体底板(340)安装有保温罐前半体(301)和保温罐后半体(300)；所述保温罐体底板(340)的底部设置有用于套装在所述滑动套管(320)上的滑座(321)；所述保温罐前半体(301)与保温罐后半体(300)在转动侧通过保温罐体折页(330)连接；所述保温罐前半体(301)与保温罐后半体(300)在开合侧设置有锁紧螺栓(350)。
  3. 根据权利要求2所述的下探式摇床，其特征在于，所述摇盘底板(218)在保温罐体的滑动路径上设置有挡块(312)，所述保温罐体底板(340)的外侧具有L型卡抵部；所述挡块(312)与所述保温罐体底板(340)外侧的L型卡抵部相适配。
  4. 根据权利要求2所述的下探式摇床，其特征在于，所述保温罐前半体(301)和保温罐后半体(300)之间设置有四个罐用定位销(303)。
  5. 一种流体循环泵，其特征在于，包括：双层硬塑摇罐(400)、搅拌罐(102)以及如权利1至4中任一项所述的下探式摇床；
    所述双层硬塑摇罐(400)设置于可开合的保温罐体中；
    所述搅拌罐的上部出水口与所述双层硬塑摇罐(400)的内罐(405)底部的两回水口(420)之间通过两回水硅胶软管(421)连接；所述搅拌罐的下部进水口与所述双层硬塑摇罐(400)的外罐(414)底部的外罐底出水口(410)之间通过出水硅胶软管(411)连接；所述搅拌罐(102)内设置有搅拌轴(108)，所述搅拌轴(108)安装搅拌桨(120)，所述搅拌轴(108)的端部安装有电机(110)。
  6. 根据权利要求5所述的流体循环泵，其特征在于，所述双层硬塑摇罐(400)包括：外罐(414)、内罐(405)和罐盖(402)；所述外罐(414)的底部中心位置设置有外罐底出水口(410)；所述外罐(414)的上部呈圆锥罐体状，所述外罐(414)的下部呈圆桶罐体状；所述外罐(414)在其上部圆锥罐***置对称设置有两个进水凸部(422)；所述外罐(414)的底部设置有四个定位柱(425)；所述外罐(414)底部的外罐底出水口(410)能从所述保温罐体底板(340)、所述摇盘底板(218)预留的安装孔中垂直向下伸出；所述内罐(405)的底部对称设置有两回水口(420)；所述内罐(405)的上部呈圆锥罐体状，所述内罐(405)的下部呈圆桶罐体状；所述内罐(405)在其上部圆锥罐***置对称设置有内罐出水口；所述内罐出水口的一侧边缘设置有内罐出水口切向流挡板(461)；所述内罐出水口的底侧边缘设置有内罐出水口下部水平流挡板(462)；所述内罐(405)底部的两回水口(420)能从所述保温罐体底板(340)、所述摇盘底板(218)预留的安装孔中垂直向下伸出；所述罐盖(402)与所述外罐(414)的法兰之间通过外罐体法兰密封胶圈(423)密封连接；所述罐盖(402)上设置有若干个空气过滤器(403)。
  7. 根据权利要求6所述的流体循环泵，其特征在于，所述内罐(405)插装于所述外罐(414)的内部，且所述内罐(405)的底部设置有定位座，所述定位座与所述外罐(414)底部定位柱(425)插装连接。
  8. 根据权利要求7所述的流体循环泵，其特征在于，
    所述出水硅胶软管(411)和两回水硅胶软管(421)之中的任意一者设置有中空纤维微滤膜柱(500)；所述中空纤维微滤膜柱(500)通过固定夹与所述搅拌罐(102)连接。
  9. 根据权利要求8所述的流体循环泵，其特征在于，包括：可移动支架(600)；所述可移动支架(600)包括：支架(601)、可移动支架底板(610)、可移动支架四走轮(620)；所述支架(601)的顶部通过设置有管卡(605)，所述管卡(605)用于穿装下探式摇床支撑轴(220)，所述摇床本体(202)安装于下探式摇床支撑轴(220)上；所述支架(601)的下部设置有可移动支架底板(610)；所述支架(601)的底部设置有可移动支架四走轮(620)。
  10. 一种大循环细胞截留装置，其特征在于，包括：上清液抽取与反冲洗***以及根据权利要求5至9中任一项所述的流体循环泵；
    所述上清液抽取与反冲洗***包括：中空纤维微滤膜柱(500)、蠕动泵(570)、隔膜泵总成(560)、保温罐(586)、上清液周转袋(580)、上清液存储袋(583)和上清液存储罐(585)；所述中空纤维微滤膜柱(500)上部有上清液抽出口(520)，所述中空纤维微滤膜柱(500)下部有上清液反冲洗入口(510)；所述蠕动泵(570)的蠕动泵软管(572)的一端与上清液抽出口(520)连接，所述蠕动泵(570)的蠕动泵软管(572)的另一端与上清液周转袋(580)的上部连接，所述上清液周转袋(580)的下部与隔膜泵总成(560)连接；所述上清液周转袋(580)的中部与上清液存储罐(585)内的上清液存储袋(583)连接；所述隔膜泵总成(560)与上清液反冲洗入口(510)连接。
PCT/CN2021/126286 2020-12-30 2021-10-26 一种大循环细胞截留装置、流体循环泵以及下探式摇床 WO2022142638A1 (zh)

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