CN204385208U - A kind of shake platform for bio-reactor - Google Patents
A kind of shake platform for bio-reactor Download PDFInfo
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- CN204385208U CN204385208U CN201420705851.1U CN201420705851U CN204385208U CN 204385208 U CN204385208 U CN 204385208U CN 201420705851 U CN201420705851 U CN 201420705851U CN 204385208 U CN204385208 U CN 204385208U
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Abstract
The utility model relates to a kind of shake platform for bio-reactor, it first movable platform (1) of side comprising stationary platform (2) and be arranged at this stationary platform (2), wherein the first movable platform (1) can become positive angle or negative angle to fluctuate relative to the plane at stationary platform (2) place.In alternate embodiment, also dispense described stationary platform (2), thus by described first movable platform (1) and the neighbour setting of the second movable platform (1 ').Shake platform of the present utility model, can produce abundanter wave type, enriched with oxygen mass transfer, and is conducive to cell being uniformly distributed in reactor, greatly can improve cell culture efficiency.
Description
Technical field
The utility model belongs to biochemical equipment field, and more specifically, the utility model relates to the shake platform for bio-reactor.
Technical background
The large class of in bio-reactor is cell culture reactor, for cultivating zooblast and vegetable cell.These cells, in the process of growth, need in liquid medium, supply enough oxygen, therefore need the gas-liquid mass transfer of managing quickening oxygen.Traditional method uses stirring rake stir culture medium, or blast oxygen bubble in developing medium, to increase gas liquid interfacial area, accelerates the gas phase of oxygen above developing medium to the diffusion liquid medium.But mechanical stirring or this Bubbling method produce higher shearing force in liquid culturing medium, cause cell injury.For this reason, since eighties of last century nineties, progressively develop wave bio-reactor, cell and developing medium are placed in aseptic disposable plastic culture bag by it, and are placed on the shake platform of particular design.The shake of platform makes developing medium produce wave, the Surface Renewal between gas-liquid is realized by wave replacement stirring and bubbling, both enriched with oxygen mass transfer, turn avoid stirring arm end of blade and bubbling to the injury of cell, the cell cultures microenvironment of the dissolved oxygen that gentle low-shearing power is simultaneously relatively high is provided, is conducive to improving cell state, improving cell density and output.
A kind of representational wave bio-reactor is the wave bio-reactor of GE Healthcare Wave ProductsGroup company of the U.S., it comprises " seesaw type " shakes platform and is placed in the cell culture bags on this shake platform, fluctuated by the seesaw type of this shake platform, wave is produced in nutrient solution, but this " seesaw type " shakes platform and integrally fluctuates around intermediate support point, the wave feature that on platform, in reactor, liquid culture is formed and admixture can only be regulated by the angle regulating platform to move up and down, liquid culture wave feature and admixture controllability less, can not undertow be formed and fully mix, oxygen is passed between solid culture and liquid in liquid, heat transfer etc. are not bery abundant, wave feature and admixture adjust alternative less.
The another kind of wave bio-reactor improved is shown in Publication about Document: Two new disposablebioreactors for plant cell culture:the wave and undertow bioreactor andthe slug bubble bioreactor, Terrier, et al., Biotehnology andBioengineering, 2006, vol.96, No.5,914-923, is incorporated to herein incorporated by reference in full by this paper.This paper describes and flexiplast biological culture bag is placed in " sit-up formula " shakes on platform, Fig. 1 of the present utility model illustrates the structure of this shake platform.This shake platform has a horizontal table dormant and is positioned at the lift platform of this horizontal table dormant side, and lift platform periodically upwards rises certain angle from the zero position with this horizontal table dormant same level and falls after rise to this zero position.Along with rising and the falling of lift platform, in flexiplast biological culture bag, produce wave, when this wave is passed to the other end of culture bag, produce undertow, back transfer, strengthens the renewal of gas-liquid surface thus." sit-up formula " platform ratio " seesaw type " should be shaken shake platform there is abundanter wave type adjustment capability.
But contriver finds in practice, this " sit-up formula " is shaken platform and also be there are some shortcomings: its wave and undertow, occur in liquid depth more at the middle and upper levels, such as between upper 1/3 supreme 1/2 of liquid depth, and lower floor in liquid, the then less impact being subject to wave and undertow.Therefore, larger cell cluster, be easy to the middle lower floor being deposited on liquid, especially lower floor in the middle position of flexiplast biological culture bag, because initial wave and undertow are all weak to this position influence, therefore have a large amount of cell clusters to be deposited on this, as shown in the cluster cell relative deposition district 5 in accompanying drawing 1 of the present utility model.Wherein " relative deposition " is not that phalangeal cell cluster is still in motionless herein, but cell cluster is not moved throughout whole culture bag, be only swing with ripple back and forth in this relative deposition district, and regeneration function that depth direction rolls dies down.Therefore, cell cluster is not well-dispersed in developing medium, and itself and this obviously reduce the utilization ratio of cell to dissolved oxygen and developing medium.
The purpose of this utility model is the problem that will solve above-mentioned cell Cluster deposition, and meanwhile, the utility model is also wished to provide to have and made more by force unrestrained ability and wave type more enriches adjustable shake platform.
Utility model content
The utility model provides a kind of shake platform for bio-reactor, it first movable platform (1) of side comprising stationary platform (2) and be arranged at this stationary platform (2), wherein, the first movable platform (1) can become positive angle or negative angle to fluctuate relative to the plane at stationary platform (2) place.
Herein, formed angle when described positive angle refers to that movable platform is positioned at above the plane at stationary platform place, described negative angle refers to formed angle below the plane that movable platform is positioned at stationary platform place.
In preferred embodiment of the present utility model, the both sides of described stationary platform (2) are respectively equipped with the first movable platform (1) and the second movable platform (1 '), and the two becomes positive angle or negative angle to fluctuate with frequency relative to the plane at stationary platform (2) place with respective independently angle.
In further preferred embodiment of the present utility model, described first movable platform (1) and the second movable platform (1 ') are independent to be separately connected by axle (7) turnably with described stationary platform (2).
In further preferred embodiment of the present utility model, described first movable platform (1) and the second movable platform (1 ') are shaken in the same way or oppositely shake.
In preferred embodiment of the present utility model, described stationary platform (2) can also be dispensed, thus by described first movable platform (1) and the neighbour setting of the second movable platform (1 ').Preferably, described first movable platform (1) and described second movable platform (1 ') are done independently of one another and are up and down reciprocatingly shaken under motor and transmission mechanism promote.
The mechanism fluctuated for the movable platform promoted in the utility model is all known, repeats no more.
In preferred embodiment of the present utility model, described bio-reactor is flexible bag-like bio-reactor (3).
Advantage of the present utility model is as follows:
Shake platform of the present utility model is than traditional seesaw type shake platform and sit-up formula shake platform, advantage is had more in the intensity producing undertow and wave type, enhance the renewal rate of gas-liquid surface, therefore the mass transfer process of oxygen from gas phase to liquid phase is enhanced, be conducive to the growth of vegetable cell to be cultivated, also be conducive to reunion and the relative deposition of avoiding cell, therefore, achieve very high cell yield.In addition; making wave because of shake platform of the present utility model acts on stronger; the cell cultures of predetermined productive rate then can be completed in shorter time; decrease the bending number of times of flexible plastic pouch; or; the liftable lower angle of movable platform, reduces flexible pouch bending angle, and it is damaged because of bending repeatedly or wide-angle bending that these benefits all can protect flexible plastic pouch more difficult.
Accompanying drawing explanation
Fig. 1 be the sit-up formula for bio-reactor of the prior art shake platform and on the structural representation of flexible bag-like bio-reactor.Wherein dotted line is depicted as another limit position of movable platform, lower same.
Fig. 2 be a type the shake platform for bio-reactor of the present utility model and on the structural representation of flexible bag-like bio-reactor, wherein movable platform becomes positive angle with stationary platform place plane.
Fig. 3 be shake platform shown in Fig. 2 and on the structural representation of flexible bag-like bio-reactor, wherein movable platform becomes negative angle with stationary platform place plane.
Fig. 4 is the structural representation of the shake platform for bio-reactor of the present utility model of another kind of type.
Fig. 5 is the wherein structural representation of the shake platform for bio-reactor of the present utility model that is omitted of stationary platform.
Description of reference numerals: 1, movable platform; 2, stationary platform; 3, flexible bag-like bio-reactor; 4, cell cluster; 5, cell cluster relative deposition district; 6, reactor cracky place; 7, axle.
Embodiment
There is provided following examples to illustrate the utility model, but limit the utility model never in any form.
In each embodiment and comparative example, the flexible plastic pouch through sterilization is all adopted to carry out culturing plants cell as bio-reactor, cell culture fluid is accommodated in bag, vegetable cell to be cultivated is Vitis, and in plastics bag, be filled with oxygen (concentration 99.9%), keep certain gaseous tension, reactor oxygen flow is entered in embodiment and comparative example, concentration, pressure, temperature is identical, go out airshed, pressure is through rate of flow meter, the measurement instruments such as tensimeter measure numerical value, by turnover oxygen flow, pressure can calculate the consumption of oxygen in the unit time (through measuring, air outlet temperature, pressure, change in concentration is very little, numerical value can be considered as identical, oxygen depletion amount in the unit time can be determined by turnover airshed numerical value, calculation formula: in certain hour, charge flow rate subtracts the difference airshed, divided by the time, obtain oxygen depletion amount in the unit time), then this flexible plastic pouch (same volume 20 liters) is placed in respectively traditional seesaw type shake platform (1# shakes platform), sit-up formula is shaken on platform (2# shakes platform) and shake platform of the present utility model (3# shakes platform and 4# shakes platform), each shake land lengths, width is identical, cultivate under the experiment condition that other starting condition are all identical except shake Platform Type is different, what every 12 hour records measured goes out airshed, pressure, concentration data, calculate the oxygen consumption rate of output inner cell accordingly.In experiment, whether there is undertow with eye observation, and the intensity of undertow, and the reunion situation of making plant cell.
Comparative example 1
The seesaw type biology shake platform of WAVE, be called that 1# shakes platform, its two ends are anti-phase in the angle of ± 15 ° to move up and down.Wherein do not observe undertow, the 6th per day oxygen-consumption is 163mg/L, and namely average often liter of cell culture fluid consumes 163mg oxygen, and cell the 6th day growth multiple is 4.2 times (see table 1).
Comparative example 2
Sit-up formula shake platform, namely adopts the shake platform of the form of " stationary platform and movable platform combine and movable platform can only move to level attitude ", and be called 2# shake platform, namely its movable platform is at 0-30 ° of range of motion.Along with the fluctuating of movable platform, observing bag inherence has undertow to exist away from movable platform one end, and about 1/2 place of the bag length that this undertow can feed through in stationary platform from undertow nidus just fades away.The 6th per day oxygen-consumption detected in experiment is 198mg/L, and this illustrates that the oxygen mass transfer efficiency ratio seesaw type shake platform in this sit-up formula shake platform increases.But find in experiment, in the liquid phase middle and lower part of culture bag middle part, there is the relative deposition district of a vegetable cell cluster, cause cell culture efficiency still not high enough, the 6th day growth multiple is 4.5 times (see table 1).
Embodiment 1
Adopt the shake platform of the present utility model of " stationary platform and movable platform combine and movable platform can move downward " form, be called 3# shake platform, its movable platform moves up and down within the scope of ± 15 °.Find have stronger undertow to occur in the bag end away from movable platform in experiment, this undertow can feed through to from undertow nidus bag length in stationary platform nearly 2/3 even 3/4 place just disappear.Detect in experiment that the 6th per day oxygen-consumption is 240mg/L, illustrate that oxygen mass transfer speed ratio sit-up formula is faster.Only observe little cell Cluster deposition in experiment, even do not deposit completely, this illustrates under strong undertow effect, and the dispersiveness of cell cluster in bag is better, and therefore the 6th day growth multiple is 5.1 times (see table 1).
Embodiment 2
Adopt the shake platform of the present utility model of " stationary platform and two movable platforms combine and movable platform can move downward " form, be called 4# shake platform, the movable platform at its two ends is anti-phase within the scope of ± 15 ° to move up and down.Find have in two ends of bag stronger undertow to occur, two-way undertow can be produced in experiment, and nearly 3/4 place that each undertow can feed through to the bag length in stationary platform from undertow nidus is long to whole bag.Detect in experiment that the 6th per day oxygen-consumption is 271mg/L, illustrate that oxygen mass transfer speed ratio 3# shaking table is faster.Almost do not observe cell cluster or depositional phenomenon in experiment, this illustrates under strong two-way undertow effect, and the dispersiveness of cell cluster in bag is better, and the 6th day growth multiple is 5.5 times (see table one).
Table 1
Note: 1. pocket type Flexible reactor volume is all 20 liters;
2. provenance: from the Vitis of same batch of shake-flask culture;
3. oxygen source: liquid oxygen vacuum jacketed flask, purity 99.9%.
4. in table, the 0th day cell net weight is originally enter reactor inner cell weight, and other net weight data are accumulative gross weight after the growth of certain hour inner cell;
5. growing multiple is certain hour inner cell growth cumulative weight, and with the ratio of the 0th day weight, numerical value larger explanation growth is faster.
More than test the sufficient proof advantage of shake platform of the present utility model.
Claims (6)
1., for a shake platform for bio-reactor, it first movable platform (1) of side comprising stationary platform (2) and be arranged at this stationary platform (2), is characterized in that:
First movable platform (1) can become positive angle or negative angle to fluctuate relative to the plane at stationary platform (2) place.
2. shake platform according to claim 1, it is characterized in that the both sides of described stationary platform (2) are respectively equipped with the first movable platform (1) and the second movable platform (1 '), the two becomes positive angle or negative angle to fluctuate with frequency relative to the plane at stationary platform (2) place with respective independently angle.
3. shake platform according to claim 1, be is characterized in that described first movable platform (1) and the second movable platform (1 ') are independent separately and is connected turnably by axle (7) with described stationary platform (2).
4. shake platform according to claim 2, is characterized in that described first movable platform (1) and the second movable platform (1 ') are shaken in the same way or oppositely shake.
5. shake platform according to claim 2, is characterized in that described first movable platform (1) and described second movable platform (1 ') are done independently of one another under motor and transmission mechanism promote and up and down reciprocatingly shakes.
6. the shake platform according to any one of claim 1-4, wherein said bio-reactor is flexible bag-like bio-reactor (3).
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| CN201420705851.1U CN204385208U (en) | 2014-11-21 | 2014-11-21 | A kind of shake platform for bio-reactor |
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| CN201420705851.1U CN204385208U (en) | 2014-11-21 | 2014-11-21 | A kind of shake platform for bio-reactor |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016078548A1 (en) * | 2014-11-21 | 2016-05-26 | 天津艾赛博生物技术有限公司 | Rocking platform for bioreactor |
| CN106754633A (en) * | 2017-02-14 | 2017-05-31 | 天津艾赛博生物技术有限公司 | A kind of regulation and control method of pilot scale culture Herba Saussureae Involueratae cell high yield flavones |
| CN108795686A (en) * | 2017-05-03 | 2018-11-13 | 莱弗斯基因股份有限公司 | Culture apparatus with rotation system and culture systems |
-
2014
- 2014-11-21 CN CN201420705851.1U patent/CN204385208U/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016078548A1 (en) * | 2014-11-21 | 2016-05-26 | 天津艾赛博生物技术有限公司 | Rocking platform for bioreactor |
| CN106754633A (en) * | 2017-02-14 | 2017-05-31 | 天津艾赛博生物技术有限公司 | A kind of regulation and control method of pilot scale culture Herba Saussureae Involueratae cell high yield flavones |
| CN108795686A (en) * | 2017-05-03 | 2018-11-13 | 莱弗斯基因股份有限公司 | Culture apparatus with rotation system and culture systems |
| CN108795686B (en) * | 2017-05-03 | 2022-09-23 | 莱弗斯基因股份有限公司 | Culture instrument with rotating system and culture system |
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Effective date of registration: 20200416 Address after: 404100 15-1, No. 6, fufu East Road, Beibu New District, Yubei District, Chongqing Patentee after: Chongqing Kairen Investment Co., Ltd Address before: Six 300457 / F, experimental building, Tianjin International Biomedical Research Institute, 220 Dongting Road, Binhai New Area, Tianjin, N602 Patentee before: TIANJIN ACELBIO Co.,Ltd. |
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Effective date of registration: 20201201 Address after: 400700 No.8 Fengqi Road, caijiagang Town, Beibei District, Chongqing Patentee after: Ansapo (Chongqing) Biotechnology Co.,Ltd. Address before: 404100 15-1, No. 6, fufu East Road, Beibu New District, Yubei District, Chongqing Patentee before: Chongqing Kairen Investment Co.,Ltd. |