CN105925481A - Full-automatic cell continuous culture system - Google Patents
Full-automatic cell continuous culture system Download PDFInfo
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- CN105925481A CN105925481A CN201610325576.4A CN201610325576A CN105925481A CN 105925481 A CN105925481 A CN 105925481A CN 201610325576 A CN201610325576 A CN 201610325576A CN 105925481 A CN105925481 A CN 105925481A
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- 239000010410 layer Substances 0.000 claims description 21
- 238000001514 detection method Methods 0.000 claims description 18
- 239000012930 cell culture fluid Substances 0.000 claims description 17
- 239000004698 Polyethylene Substances 0.000 claims description 14
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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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/14—Bags
-
- 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/16—Vibrating; Shaking; Tilting
-
- 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
- C12M31/00—Means for providing, directing, scattering or concentrating light
- C12M31/10—Means for providing, directing, scattering or concentrating light by light emitting elements located inside the reactor, e.g. LED or OLED
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- 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
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- 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/26—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pH
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- 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/48—Automatic or computerized control
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Abstract
The invention provides a full-automatic cell culture system, which at least comprises a control module, a control platform, a dark-field microscope for online observation of cell culture, a cell culture shaking table and a cell culture bag, wherein the cell culture shaking table comprises a culture bag bracket, a shaking rack and a shaking device; the culture bag bracket is provided with an arc-shaped base plate and cell culture bag fixing parts; an objective lens inserting notch is formed in the arc-shaped base plate; the cell culture bag comprises a sealed bag body, and a transparent viewing region is formed in the middle of the bottom surface of the bag body; the bag body is arranged on the cell culture shaking table, and the position of the transparent observation region is consistent with the position of the objective lens notch; according to the dark-field microscope for online observation of cell culture, an objective lens can be just inserted in the objective lens inserting notch in the cell culture shaking table; the control platform is connected to the dark-field microscope for online observation of cell culture and the cell culture shaking table; and the control module is connected to the control platform. With the application of the full-automatic cell culture system disclosed by the invention, cell continuous culture and observation can be achieved; and the full-automatic cell culture system is convenient and rapid, and the efficiency of cell culture can be greatly improved.
Description
Technical field
The present invention relates to a kind of full-automatic cell continuous culture system, be mainly used in cultivating and observation of cell.
Background technology
The immunocyte being presently used for human body therapy is cultivated, and mainly or uses Tissue Culture Dish under the super-clean bench of laboratory
Or blake bottle cultivates, and according to the density of cell growth, carry out continuous sub-bottle cultivation, this cell training mode, not only
Take time and effort, simultaneously because need different sub-bottle, sample-adding, be easier to pollute.Meanwhile, current use for laboratory is in sight
The method examining cell is the most original, mostly includes sampling and makes the link of sample, operating relatively complicated, it is impossible to realize cell
Continuously and Real Time Observation.
Along with development and the progress of artificial intelligence of science and technology, cultivation and the observation continuously of cell have begun to by people institute
Pay close attention to, but a kind of device cultivated continuously and observe that can realize cell does not also occur.
Summary of the invention
The shortcoming of prior art in view of the above, it is an object of the invention to provide a kind of full-automatic cell and cultivates continuously
System, it is possible to achieve cultivating continuously and observation of cell, and the mensuration of the parameters to nutrient solution.
For achieving the above object and other relevant purposes, the present invention provides a kind of full-automatic cell culture systems, described carefully
Born of the same parents' culture systems at least includes: control module, control platform, the dark ground microscope for the online observation of cell cultivation, cell
Cultivate shaking table, cell culture bags and power module；
Described cell culture table includes that culture bag bracket, rocking carrier and agitating device, described culture bag bracket are provided with arc
Shape base plate and cell culture bags fixed component, described rocking carrier includes that swinging base, described swinging base are provided with support arm, institute
Stating culture bag bracket and described rocking carrier and be connected through support arm is fixing, described agitating device includes that pedestal, pedestal are provided with and waves
Assembly, described swinging base is connected with waving assembly, and described curved plate is provided with object lens and inserts breach；
Described cell culture bags, including closed bag, is provided with transparent observing district in the middle part of the bottom surface of described bag；Described bag
Body is placed in cell culture table, and described transparent observing district is consistent with object lens gap position；
The described dark ground microscope cultivating online observation for cell, including object lens, described object lens just can be inserted into carefully
Born of the same parents cultivate the object lens on shaking table and insert breach；
Described control platform is connected to cell respectively and cultivates the online dark ground microscope observed and cell culture table；
Described control module connects control platform；
Described power module is that whole system is powered.
For further optimizing design scheme, the described dark ground microscope for the online observation of cell cultivation includes illumination
Element, Moveable support, support base, photo-sensitive cell, caliber unit, A/D converting unit, power module and control mould
Block, described illumination component is arranged on the top of Moveable support, and described Moveable support is arranged on support base, described
Caliber unit is connected to Moveable support bottom, and described object lens are arranged on caliber unit and corresponding under illumination component
Side, described photo-sensitive cell connects sense for the light signal gathering on object lens, described A/D converting unit in being arranged on caliber unit
Optical element, described control module connects A/D converting unit.
Preferably, described illumination component include circle lamp socket, and be arranged on lamp socket surround several concentric circles row
The concentrically ringed center of circle described in the illuminating lamp of row is consistent with the home position of lamp socket.
Preferably, described lamp socket is 10-30 centimetre to the distance of object lens.
Preferably, the light source of described illuminating lamp forms dark field with object lens, meets the needs of dark field illumination.
Preferably, described illuminating lamp is LED.
Preferably, described support base include stepper motor, slide mechanism and base, described slide mechanism include slide block with
Slide rail, described control module connects and controls stepper motor, described stepper motor connection sliding block, and described slide block slides even through slide rail
Being connected on base and horizontally moveable, described Moveable support is arranged on slide block.
For further optimizing design scheme, described curved plate arranges one or more accessory fixed hole position, described
The space for installing or insert outside appurtenances is left under accessory fixed hole position.
Preferably, described curved plate is provided with heating plate.
Preferably, the edge of described curved plate is provided with baffle plate.
Preferably, described cell culture bags fixed component is located at the both sides of curved plate, including lateral from curved plate two
The platform that both sides extend, described platform is provided with hold-down bars fixture and/or hold-down bars interposer.
Preferably, described swinging base is flat board, and two ends are provided with support arm, and culture bag bracket does not contacts with swinging base,
Between leave space with install or insert outside appurtenances.
Preferably, described in wave assembly and include hinged seat and at least one mechanism that pumps, described hinged seat sets
On pedestal, described swinging base is hinged with hinged seat, described in the mechanism that pumps be connected with swinging base or compress mutually.
For further optimizing design scheme, described cell culture bags includes: the fixed component of bag both sides, described closing
Formula upper face of bag body is provided with outside liquid adding mouth, outside liquid injection port, gas feed and gas vent, described closed bag
Bottom surface is provided with liquids recovery mouth and at least one sensor connector, described outside liquid adding mouth, outside liquid injection port, gas
It is equipped with aseptic snap joint on import, gas vent and liquids recovery mouth.
Preferably, described closed bag is surrounded a solid jointly by upper bag sheet, lower bag sheet, left side bag webs and right side bag webs
Bag chamber, the bottom of described left side bag webs and described right side bag webs is curved, described left side bag webs and described right side bag webs all in
Ellipse, described upper bag sheet and lower bag sheet are rectangular.
Preferably, described closed bag innermost layer is polyethylene layer.
Preferably, the material used by described closed bag is five layers of composite construction, be followed successively by from the inside to the outside polyethylene layer,
Adhesive layer, ethylene, propylene alcohol layer, adhesive layer and polyethylene layer.
Preferably, described sensor connector is provided with one or more.
Preferably, described sensor connector is noncontacting proximity sensor joint or touch sensor joint.
Preferably, described contactless sensor connector includes basal disc and sensor probe accommodating cavity, on described basal disc
Being provided with transparent partition, described sensor probe accommodating cavity is connected with described basal disc and is positioned at the side of described transparent partition, described
The opposite side of transparent partition is provided with conversion film.
Preferably, described film of changing causes color-changing membrane or dissolved oxygen cause color-changing membrane into pH.
For further optimizing design scheme, described control platform includes switch board, and be arranged on switch board from
Dynamic heating unit, preheating bag and peristaltic pump；Described automatic heating unit arranges and includes that preheating table, described preheating bag are arranged on preheating
On plate, described peristaltic pump includes that the first peristaltic pump and the second peristaltic pump, described automatic heating unit also include cell culture fluid tank
Body, described tank body is by the inlet of the first pipeline communication preheating bag, and the outlet of described preheating bag is thin by second pipe connection
Born of the same parents' culture bag, described first peristaltic pump connects the first pipeline, and described second peristaltic pump connects second pipe, described automatic heating list
Unit, the first peristaltic pump and the second peristaltic pump link control module.
Preferably, being additionally provided with gas mixing units inside described switch board, the gas outlet of described gas mixing units is arranged
Upper at switch board, and by the 3rd pipeline communication cell culture bags, the air inlet of described gas mixing units connects outside gas
Source, described gas mixing units link control module.
Preferably, described switch board being additionally provided with pH value detection tabs and dissolved oxygen detection tabs, the detection of described pH value is visited
Head and dissolved oxygen detection probe.
For further optimizing design scheme, in order to realize the control module control to whole culture systems, described control
Module includes:
Moveable support control unit, for controlling the movement of Moveable support；
Illumination component control unit, for controlling the switch of illumination component；
Check unit, for checking the content that under current state, object lens are observed, and cell growth under current state
The parameters of environment；
Storage element, for storing the content observed needing to preserve and every ginseng of record cell growing environment
Number；
Gas control unit, for controlling the gas in cell culture bags；
Cell culture fluid control unit, for controlling temperature and the supply of cell culture fluid.
Another aspect of the present invention there are provided the application cultivating the online dark ground microscope observed for cell:
For observation of cell culture bag.
Another aspect of the present invention there are provided cell culture bags application: for cultivating cell.
As it has been described above, the full-automatic cell continuous culture system of the present invention, have the advantages that
(1) realize the continuous cultivation of cell, heat simultaneously, rock, being carried out continuously of being loaded；
(2) without manually changing liquid, the temperature for cell liquid can realize intelligent control, it is possible to achieve automatic liquid-feeding；
(3) user can be according to the status adjustment shaking table wobble frequency of cell cultivation and angle, it is ensured that cell is in optimal
Growing environment；
(4) it is provided with multiple fixed hole position due on curved plate in the present invention, it is thereby achieved that various detector
Probe the various parameters in cell culture bags are detected；
(5) the online dark ground microscope observed is cultivated for observation of cell sample for cell, it is not necessary to sampling, Ke Yishi
The continuous Real Time Observation of existing cell；
(6) the cell culture bags structure of the present invention is unique, can meet and persistently be loaded cultivation under the conditions of a small amount of nutrient solution, directly
To reaching cultivation demand；
(7) the 3D heterocyst culture bag of present invention design, in cell cultivation process, the shake of cultivation platform is produced
Shearing force is minimum, and the shearing force damage causing cell is also minimum；
(8) all joints of the cell culture bags of the present invention use the aseptic mode that connects soon, decrease cultivation behaviour to greatest extent
Make the risk of the cell contamination caused；
(9) volume of the cell culture bags of the present invention infinitely can expand according to the amount of required cultivation；
(10) control system utilizing the present invention can record and various parameters in real time inspection cell growth process；
(11) the intelligent gas provided needed for cell cultivation.
Accompanying drawing explanation
Fig. 1 is shown as the schematic diagram of preferred embodiment of the present invention cell culture table.
Fig. 2 is shown as the present invention preferred culture bag bracket schematic diagram.
Fig. 3 is shown as another preferred culture bag bracket schematic diagram of the present invention.
Fig. 4 is shown as the schematic diagram of another preferred embodiment cell culture table of the present invention.
Fig. 5 is shown as the schematic diagram of further embodiment cell culture table of the present invention.
Fig. 6 is shown as in the present invention cultivating the online dark ground microscope structural representation observed for cell.
Fig. 7 is shown as dark field illumination principle schematic in the present invention.
Fig. 8 is shown as the cell culture bags end face schematic diagram of the embodiment of the present invention.
Fig. 9 is shown as the cell culture bags schematic bottom view of the embodiment of the present invention.
Figure 10 is shown as the cell culture bags Bag structure schematic diagram of the preferred embodiment of the present invention.
Dotted line index wire points to the bag that illustrated angle theory is blocked
Figure 11 is shown as the cell culture bags of the preferred embodiment of the present invention and uses the signal of state lower bag body end face connecting line
Figure.
Figure 12 is shown as the cell culture bags of the preferred embodiment of the present invention and uses the connecting line signal of state lower bag body bottom surface
Figure.
Figure 13 is shown as the sensor connector profile of the preferred embodiment of the present invention.
Figure 14 is shown as control module structural framing figure.
Figure 15 is shown as whole system structural representation.
1 culture bag bracket
11 curved plates
111 accessory fixed hole positions
112 object lens insert breach
113 baffle plates
114 heating plates
12 cell culture bags fixed components
121 platforms
122 hold-down bars fixtures
123 hold-down bars interposers
2 rocking carriers
21 swinging bases
211 support arms
3 agitating devices
31 wave assembly
311 hinged seats
312 pump mechanism
32 pedestals
4 cell culture bags
41 closed bags
411 outside liquid adding mouths
412 outside liquid injection ports
413 gas feeds
414 gas vents
415 liquids recovery mouths
4161 upper bag sheets
4162 lower bag sheets
Bag webs on the left of in the of 4163
Bag webs on the right side of in the of 4164
417 sensor connector
4171 for accessing the sensor connector of pH sensor probe
4172 are used for accessing the sensor connector of dissolved oxygen (DO) sensor probe
41701 basal discs
41702 sensor probe accommodating cavities
41703 transparent partitions
418 aseptic snap joints
419 transparent observing districts
42 fixed components
431 silicone tubes
432 female Luer
433 threeways
434 needleless samplers
435 air cleaners
436 air cutoff valves
437 folders
438 bands
44 seal areas
5 support base
501 stepper motors
502 slide blocks
503 bases
6 caliber unit
61 object lens
7 control modules
8 lamp sockets
9 Moveable supports
10 photo-sensitive cells
13 switch boards
1301 first peristaltic pumps
1302 second peristaltic pumps
1303 pH detection tabs
1304 dissolved oxygen detection tabs
1305 gas vents
1306 external cellular nutrient solutions
1307 second pipes
1308 first pipelines
1309 preheating bags
Detailed description of the invention
By particular specific embodiment, embodiments of the present invention being described below, those skilled in the art can be by this explanation
Content disclosed by book understands other advantages and effect of the present invention easily.
Refer to Fig. 1 to Figure 15.It should be clear that structure depicted in this specification institute accompanying drawings, ratio, size etc., the most only use
To coordinate the content disclosed in specification, understanding for those skilled in the art and read, being not limited to the present invention can
The qualifications implemented, therefore do not have technical essential meaning, the modification of any structure, the change of proportionate relationship or the tune of size
Whole, under not affecting effect that the present invention can be generated by and the purpose that can reach, all should still fall in disclosed skill
In the range of art content obtains and can contain.Meanwhile, in this specification cited as " on ", D score, "left", "right", " middle " and
The term of " one " etc., is merely convenient to understanding of narration, and is not used to limit the enforceable scope of the present invention, its relativeness
It is altered or modified, without, under essence change technology contents, raising when being also considered as the enforceable model of the present invention.
Seeing Figure 15, the invention discloses a kind of full-automatic cell culture systems, cell culture system at least includes: control
Module, control platform, cultivate online dark ground microscope, cell culture table, cell culture bags and the electricity observed for cell
Source module, control module connects control platform, controls platform and connects and control cell culture table respectively and train for cell
Support the dark ground microscope of online observation, cultivate the online dark ground microscope observed for cell and shake for observation of cell cultivation
The cell cultivated on bed, described cell culture bags is arranged in cell culture table, and described power module is that whole system is powered.
Embodiment 1 cell culture table
Cell culture table as shown in Figure 1, including culture bag bracket 1, rocking carrier 2 and agitating device 3, described culture bag
Bracket 1 is provided with curved plate 11 and cell culture bags fixed component 12, and described rocking carrier 2 includes swinging base 21, described in wave
Base 21 is provided with support arm 211, and described culture bag bracket 1 and described rocking carrier 2 are connected through support arm 211 is fixing, described in shake
Dynamic device 3 includes pedestal 32, and pedestal is provided with and waves assembly 31, and described swinging base 21 is connected with waving assembly 31.
In preferred embodiment as shown in Figure 2, described curved plate 11 is provided with object lens and inserts breach 112.In order at cell
Real Time Observation cell situation in cultivating continuously, is provided with transparent observing district bottom culture bag, and object lens insert breach 112 and mate transparent
Observation area, can be inserted into object lens, thus utilizes object lens, directly the cell situation in the observation of cell culture bag of bottom.
Described curved plate 11 is for housing the main part of arc 3D cell culture bags 4.The design of curved plate makes
Arc 3D cell culture bags is in cell cultivation process, and bottom can maintain arc, thus in cell cultivation process, cultivation platform
The produced shearing force of shake minimum, the shearing force damage causing cell is also minimum.
It is also preferred that the left described curved plate dual-side is arc.
Further, as in figure 2 it is shown, one or more accessory fixed hole position 111 can be arranged on described curved plate 11.
It is also preferred that the left described fixed hole position 111 is provided with internal thread preferably to fix outside appurtenances.Outside appurtenances can be various spy
Survey the probe of device, as pH value and oxygen dissolving value detect probe etc..Outside appurtenances can also be various outside liquid feed tube, injection unit
Part, drain pipe, extraneous gas conveying pipe etc. is easy to the accessory that cell is cultivated continuously.
Described curved plate is the arc of concave downward in a state of use.Further, described object lens insert breach 112
It is arranged at the concave bottom region of curved plate.
Further, in preferred embodiment as shown in Figure 2, the edge of curved plate 11 is provided with baffle plate 113.Baffle plate can prevent
Cell culture bags slips in culture bag bracket, shifts.
In preferred embodiment as shown in Figure 3, described curved plate 11 is provided with heating plate 114.Heating plate can be trained at cell
Heating when supporting, thinking that cell is cultivated provides suitable temperature.Control module can set the temperature needed for cell culture bags 4,
Control the heating of heating plate.
As in figure 2 it is shown, described cell culture bags fixed component 12 may be provided in the both sides of curved plate, can be from arcuate bottom
The platform 121 that plate both sides of the edge extend to both sides, which is provided with the parts matched with the fixed component in cell culture bags.Example
As can be the parts fixing by mechanical force, viscous force, magnetic force etc., or screw be set on platform 121 and nut will be thin
Born of the same parents' culture bag 4 is fixed on platform.In embodiment as shown in Figure 4, cell culture bags 4 both sides are provided with hold-down bars, now,
Hold-down bars fixture 122 and/or hold-down bars interposer 123 can be provided with on platform, thus realize fixing with cell culture bags 4
The detachable connection of rod.
In described rocking carrier 2, the design of support arm 211 can play the effect holding in the palm high culture bag bracket 1.Culture bag bracket 1
Accessory fixed hole position should leave the space for installing or insert outside appurtenances for 111 times.In rocking carrier, support arm can conduct
A part for swinging base 21 is one-body molded with swinging base, can act also as single parts be arranged on swinging base it
On, or can also be one-body molded with culture bag bracket 1.On the one hand support arm can be the company of cell culture bags and outside appurtenances
Connect headspace, on the other hand, due to the high culture bag bracket 1 of frame, it is only necessary to swinging base 21 to be provided small size shaking
Pendulum power, culture bag bracket 1 just can one in a big way in swing.
In the preferred embodiments as shown in Fig. 1,4,5, swinging base 21 is flat board, and two ends are provided with support arm 211, culture bag
Bracket 1 does not contacts with swinging base 21, between leave space with install or insert outside appurtenances, including various probes, object lens.
The described assembly 31 that waves can be the most existing mechanism realizing rocking action.
In preferred embodiment as shown in Figure 1, described in wave assembly 31 and include hinged seat 311 and at least one is upper and lower
Reciprocating mechanism 312, described hinged seat 311 is located on pedestal 32, and the swinging base 21 of rocking carrier 2 is hinged with hinged seat 311,
Thus a swing center is provided, described in the mechanism 312 that pumps be connected with swinging base 21 or compress mutually so that
Pump mechanism 312 can promote swinging base 21 around swing center make reciprocating swing motion.
Described hinged seat 311 can have one or more, and in example as shown in Figure 5, at the middle part of pedestal 32, symmetry sets
Put two hinged seats 311, so that wave more stable.Work based on the mechanism 312 that pumps, rocking carrier is permissible
Make yaw movements.
The described mechanism 312 that pumps can be various existing to realize reciprocating mechanism, the most electronic
Push rod, linear electric motors, toggle etc..Concrete, such as, described in the mechanism 312 that pumps can include motor
And cam, described motor cam is fixed on the output shaft of motor, and cam and swinging base 21 directly compresses or mutually through can be
The push rod moved up and down in guide groove compresses or hinged mutually.The motor of mechanism 312 of pumping is placed in pedestal 32.
The described mechanism 312 that pumps can be one or more.Under normal circumstances, the machine that pumps
Structure 312 can meet swing demand.Wave design based on such, can be pumped the most past of mechanism by adjustment
Multiple motion frequency, or adjust the distance between mechanism and hinged seat that pumps, waving of shaking table can be adjusted easily
Amplitude and frequency.
During work, under motor drives, the mechanism 312 that pumps promotes swinging base 21 to wave fortune around hinged seat
Dynamic, and then drive the culture bag bracket 1 being fixed on support arm 211 to drive cell culture bags 4 to rock.Bracket passes through heating plate pair
Cell is cultivated and is heated, and can access respectively by being arranged at the accessory fixed hole position 111 of bracket base in cell culture bags
Plant monitoring probe, detect cell cultivation conditions.In incubation, also can stop rocking, the object lens at bracket insert breach 112 and insert
Enter object lens direct observation of cell situation.
Embodiment 2 cultivates the online dark ground microscope observed for cell
See Fig. 6, the present embodiment also discloses a kind of dark ground microscope cultivating online observation for cell, microscope
Include but not limited to: illumination component, Moveable support 9, support base 5, object lens 61, photo-sensitive cell 10, caliber unit 6, A/D
Converting unit, control module.Illumination component is arranged on Moveable support 9 top, Moveable support 9 is arranged on support base
On 5, caliber unit 6 is arranged on Moveable support 9 bottom, and object lens 101 are arranged on caliber unit 6 and corresponding at illumination component
Lower section, photo-sensitive cell 10 is arranged in caliber unit 6 for gathering the light signal on object lens 61, and A/D converting unit connects
Photo-sensitive cell 10 and support base 5, control module connects A/D converting unit.
Photo-sensitive cell uses ccd sensor in the present embodiment, the image letter that ccd sensor is obtained by A/D converting unit
Number pass to control module.Control module also include setting in a computer check unit, be used for checking object lens under current state
The content observed, and storage element, for storing the content observed needing to preserve.
In the present embodiment, illumination component is arranged on the top of Moveable support 9, and illumination component includes but not limited to circle
The lamp socket 8 of shape and be arranged on the LED surrounding 5 concentric arrays on the lamp socket 8 of circle, between lamp socket to object lens away from
From for 18 centimetres, general could be arranged to 10-30 centimetre.Ten to 20 LED are included, for whole on each concentric circles
Individual device provides light source.On each concentric circles, the lamp on circumference can be opened simultaneously or close.
As it is shown in fig. 7, for the illumination meeting dark field, the light that illumination component sends and the angle of object lens 61 trunnion axis
Less than angle A, described angle A is the light angle with object lens 61 trunnion axis in the bosom of illumination component.
In the present embodiment, supporting base 5 and include stepper motor 501, slide mechanism and base 503, slide mechanism includes
Slide block 502 and slide rail, slide block 502 is connected on base 503 through slide rail, and stepper motor 501 link control module is also located at the end
One end of seat 503, slide block 502 connects stepper motor 501, and Moveable support 2 is arranged on slide block 502.This area common
Skilled person will understand that stepper motor 501 can use the most common stepper motor 501 to realize, stepper motor 501
Can the moving and then the relative position of whole microscopical Moveable support 9 changed of band movable slider 502.
In the present embodiment, caliber unit 6 is slidably connected on Moveable support 9, and caliber unit 6 connects packaged type
Being provided with chute at support 9, caliber unit 6 can slide up and down along chute, and on Moveable support, the relative both sides of 9 are arranged
Through hole, two through holes are respectively provided with screw, when needs regulation raises caliber unit 6, can unclamp screw, mobile caliber list
Unit 6, when being adjusted to appropriate location, tightens screw.Certainly this raises and the regulation of reduction is the trickleest regulation, maximal regulated
Scope is 5 centimetres.Known to can certainly using on other markets, the device of similar buckle is for playing fixing effect.When
So, control module 7 can also be utilized as required to control the switch of LED, with the needs of satisfied observation.
In another embodiment, Moveable support 9 has hollow structure, the illumination component control unit of control unit 7
Arrange in hollow structure.
Those skilled in the art all understands, and module controlled as described above obtains about the process controlling illumination component, CCD
Process and the process of the movement of control support base 5 that the picture signal obtained converts all can utilize calculating of the prior art
Machine, integrated circuit modules, PLD, other hardware or existing software module realize.
Use this device when observing sample, there is big advantage.When observing sample, utilizing control module 7 to move can
Whole culture vessel is placed between illumination component and object lens 61 by removable support 9, and object lens 61 are by cell culture table object lens
Insert breach 112 carry out observation of cell, utilize control module to move Moveable support 9, make it away from culture vessel, when needs again
The position then utilizing control module to move movable supporting frame 9 during secondary observation.
Embodiment 3 cell culture bags
As shown in FIG. 8 and 9, cell culture bags 4, including: closed bag 41 and the fixed component 42 of being located at bag both sides,
Described closed bag 41 end face is provided with outside liquid adding mouth 411, outside liquid injection port 412, gas feed 413 and gas
Outlet 414, described closed bag 41 bottom surface is provided with liquids recovery mouth 415 and at least one sensor connector 417, described outside
It is all provided with on liquid adding mouth 411, outside liquid injection port 412, gas feed 413, gas vent 414 and liquids recovery mouth 415
There is aseptic snap joint 418.
Cell culture bags 4 end face is provided with outside liquid adding mouth, outside liquid injection port, gas feed and gas vent
Even if in order to meet cell cultivate during be not to move out culture apparatus in the case of, also can meet interpolation cell culture fluid,
Gas needed for outside liquid (such as penicillin solution, Streptomycin Solution, inoculation liquid etc.), and offer cell cultivation divides (as provided
Carbon dioxide) needs.Cell culture bags bottom surface is provided with liquids recovery mouth can be in the case of being not to move out culture apparatus, also can be complete
Portion or part change nutrient solution.Cell culture bags bottom surface is provided with sensor connector, can be used for connecting sensor with monitoring cell training
Index of correlation in nutrient solution bag.
Snap joint refers to that the instrument that need not can be achieved with the joint that pipeline is switched on or switched off.Aseptic snap joint used is i.e.
For conventional aseptic snap joint, commercially available acquisition.Aseptic snap joint is solderable or is welded on bag.
Described closed bag can be made up of flexible material.Described flexible material is deformable material after referring to stress
Matter.It is also preferred that the left material used by described closed bag is composited by PE and EVOH.
In a preferred embodiment, the material used by described closed bag is multi-layer compound structure.Preferably, described envelope
Enclosed bag innermost layer is polyethylene (PE) layer.Innermost layer is that layer of abutment nutrient solution, and contact nutrient solution is stable
PE material, low leachable, without animality originate.
In being more highly preferred to embodiment, the material used by described closed bag is five layers of composite construction, depends on from the inside to the outside
Secondary for polyethylene (PE) layer, adhesive layer, ethylene propylene enol (EVOH) layer, adhesive layer and polyethylene (PE).These type of five layers of composite junctions
The material of structure is prior art, commercially available acquisition.
The bag webs thickness constituting sealed bag can be conventional, have employed 0.325mm in a preferred embodiment.The present invention
Cell culture bags can carry out disinfection sterilizing with gamma-rays, irradiation dose >=25Gy ,≤50Gy.The method of available heating carries out close
Envelope.
In the preferred embodiment of the invention, described closed bag by upper bag sheet 4161, lower bag sheet 4162, left side bag
Sheet 4163 and right side bag webs 4164 surround a stereoscopic bag chamber jointly.More preferred, described left side bag webs 4163 and described right side
The bottom of bag webs 4164 is curved.The 3D shape that base cambered design can make cell culture bags be formed after inflation is being cultivated
In the shake of platform, produced shearing force is less, and the shearing force damage causing cell is also down to minimum.As shown in Figure 10
Embodiment in, described left side bag webs 4163 and the equal ovalize of described right side bag webs 4164, described upper bag sheet 4161 and lower bag
Sheet 4162 is rectangular.
In preferred embodiment as shown in Figure 9, in the middle part of the bottom of described bag 41, it is provided with transparent observing district 419.Transparent sight
Cha Qu is located at the bottom of cell culture bags, can be by setting cellular morphology finder on cultivation platform and direct from bottom
Cell situation in observation of cell culture bag.
Described sensor connector can be provided with one or more.It is also preferred that the left the preferred embodiment as shown in Fig. 9 and 12
In, it being provided with two sensor connector, one of them is the sensor connector 4171 for accessing pH sensor probe, another
For being used for accessing the sensor connector 4172 of dissolved oxygen (DO) sensor probe.
Sensor connector can be the sensor connector of contact also can be contactless sensor connector.The most real
Executing in example, sensor connector is contactless sensor connector, i.e. sensor probe after inserting described sensor connector, visits
Head with the nutrient solution in bag not in contact with.
In preferred embodiment as shown in figure 12, described contactless sensor connector includes basal disc as shown in figure 13
41701 and sensor probe accommodating cavity 41702, the middle part of described basal disc is provided with transparent partition 1703, and described sensor probe holds
Put the side that chamber 1702 is connected with described basal disc 41701 and is positioned at described transparent partition 41703, the opposite side of described transparent partition
(seeing shown by arrow to point to) is provided with conversion film.To the sensor connector for accessing pH sensor probe, described conversion film
Color-changing membrane is caused for pH.PH causes color-changing membrane and can be obtained by masking after pH indicator and filmogen mixture.Described pH causes color-changing membrane and belongs to
In the pH sensing membrane etc. that prior art, such as pH electrode are used.To the sensor connector for accessing dissolved oxygen sensor probe, institute
State and change film into dissolved oxygen cause color-changing membrane.Dissolved oxygen causes color-changing membrane and can be obtained by masking after dissolved oxygen indicator and filmogen mixture
?.Described dissolved oxygen causes color-changing membrane and belongs to prior art.
Through described sensor connector, in cell culture bags, pH and the dissolved oxygen situation of nutrient solution are both transferred to color letter
Number, by accessing RGB sensor in sensor connector, color signal can be read, thus according to conversion film color and pH
Value and the relation of dissolved oxygen, it is thus achieved that the pH value of cell culture fluid and oxygen dissolving value.The result of sensor connector detection all can transmit to control
Molding block, for recording and checking.
Noncontacting proximity sensor probe with the use of RGB color sensor without sterilization, not only operate the most square
Just, and can more preferable Pollution protection.
The sensor connector of described contact can be normal sterile snap joint, can directly grafting or threaded sterilization
PH sensor or the probe of dissolved oxygen sensor.Aforementioned noncontacting proximity sensor joint also can be made after removing transparent partition and conversion film
Sensor connector for contact.
Described fixed component 42, for coordinating fixing described cell culture bags in cultivation platform, can use existing
The various parts that Sheng liquid bag can be made to fix to realize the fixing of cell culture bags, such as, can be single use and can realize admittedly
Fixed parts, such as, carry sticking parts etc., also needs to coordinate with the coalignment arranged on cultivation platform to play admittedly
The parts being set for, the parts etc. such as fixed by mechanical force, viscous force, magnetic force.In embodiment as shown in Figure 10, described solid
Limiting-members is hold-down bars, and described hold-down bars can be removable with the hold-down bars fixture set up on cultivation platform or hold-down bars interposer
Formula of unloading connects, such that it is able to reach the purpose of immobilized-cell culture bag.
Further, the two ends of described bag 41 are provided with seal area 44, and described hold-down bars is placed in seal area.
The cell culture bags of the present invention in use, can be fixed on cultivation platform by fixed component 42, be trained by cell
Support the outside liquid adding mouth 411 of bag, outside liquid injection port 412, gas feed 413, gas vent 414, liquids recovery mouth
415, by aseptic snap joint, are connected with the device providing outside liquid, gas or withdrawal liquid, gas, institute the most by the road
State the probe of grafting respective sensor in sensor connector.During cultivating cell, add outer liquid the most as required
Body, changes nutrient solution, it is provided that suitably cell cultivates atmosphere, and monitors the situation of cell culture fluid and the growing state of cell.
Concrete, described outside liquid adding mouth 411 can as shown in figure 11, outside aseptic snap joint 418 rapid abutting joint
Portion's pipeline, described exterior line can include silicone tube 431, female Luer 432 successively, and then externally connected liquid provides dress
Put, further silicone tube can access threeway 433 to connect multichannel outside liquid memory cell.
Described outside liquid injection port 412 can as shown in figure 11, through aseptic snap joint 18 rapid abutting joint exterior line, institute
State exterior line and can include silicone tube 431, female Luer 432, needleless sampler 434 successively, and then outside liquid offer is provided
Device.
Described gas feed 413 can as shown in figure 11, through aseptic snap joint 418 rapid abutting joint exterior line, described outside
Portion's pipeline can include silicone tube 431, air cleaner 435 successively, and then connects extraneous gas offer device.
Described gas vent 414 can as shown in figure 11, through aseptic snap joint 418 rapid abutting joint exterior line, described outside
Portion's pipeline can include silicone tube 431, air cleaner 435, silicone tube 431, air cutoff valve 436 successively, so with extraneous or
Gas collecting apparatus communicates.
Described liquids recovery mouth 415 can be through aseptic snap joint 418 rapid abutting joint exterior line, described as shown in figure 12
Exterior line can include silicone tube 431 and female Luer 432 successively, and then connects outside liquid collector.
Sheet folder 437 can be arranged on the silicone tube of pipeline can be sealed even by band 438 with control turnover sample, pipeline components
Connect.
About the cell culture bags in the present invention, following cell fostering requirement can be met:
(1) meet and be changed without continuous condition of culture: cell is initial to be cultivated, and measures less, along with Cell Culture Cells density
Increase, need to uninterruptedly increase cell culture fluid；The cell culture bags of the present invention can meet the initiator cell less situation of cultivation amount
Under, also can cultivate in cell culture bags；
(2) temperature conditions that cell is cultivated is met: the initial amount no matter cell is cultivated is how many, all can be with the cell of the present invention
Culture bag is cultivated, and cell culture bags can be carried out heat treatment；
(3) meet cell cultivate the condition such as pH, dissolved oxygen (DO): the design of 3D culture bag, can connect cell cultivate necessary
Gas device, and carry out the pH value of nutrient solution and the revision of dissolved oxygen by adjusting gaseous environment；
(4) non-contacting pH in cell cultivation process, dissolved oxygen detection are met: special harmless by arranging in culture bag
Avirulent photochemical reaction material, carries out the pH of nutrient solution, the monitoring of dissolved oxygen (DO) through cell culture bags；
(5) meet cell cultivate aseptic condition: total interface in culture bag, nutrient solution import, the interface of recovery tube, gas
Body is imported and exported, and all carries out aseptic rapid abutting joint mode, and gas inlet and outlet is fitted with pneumatic filter, it is ensured that cell is cultivated and is in
Germ-free condition.
(6) in the case of cell culture apparatus rocks, the shearing force suffered by cell in culture bag is the least, favorably
Growth in cell.
Embodiment 4 controls platform
In the present embodiment, control platform and include that controlling platform includes switch board 13, and be arranged on switch board 13
Automatically heating unit, preheating bag 1309 and peristaltic pump；Automatically heating unit includes preheating table, and described preheating bag 1309 is arranged on pre-
On hot plate, peristaltic pump includes the first peristaltic pump 1301 and the second peristaltic pump 1302, and the entrance of preheating bag 1309 is by the first pipeline
1308 connection external cellular nutrient solutions 1306, the outlet of preheating bag 1309 connects cell culture bags by second pipe 1307, the
One peristaltic pump 1301 connects the first pipeline 1308, and the second peristaltic pump 1302 connects second pipe 1307, automatic heating unit, first
Peristaltic pump 1301 and the second peristaltic pump 1302 link control module.
In the present embodiment, switch board 13 has well-regulated cube structure exactly, can house various work inside it
Unit and integrated circuit.Wherein, preheating table is arranged at the top of switch board 13, and it arranges preheating bag 1309.The work of preheating table
Be bag 1309 to preheating in cell culture fluid heating.Cell culture fluid uses sale on market, is suitable for the training of this cell
Support required model.The volume of preheating bag 1309 is traditionally arranged to be 500ml.Automatically heating unit link control module, so can
To set a certain specific temperature, when the temperature of the cell culture fluid preheated in bag 1309 is less than this temperature, will be automatic
Utilizing preheating table to heat to preheating bag 1309, when reaching this temperature, heating stops.First peristaltic pump 1301 is by outside cell
Nutrient solution pumps into preheating bag 1309, and the cell culture fluid reaching a certain specified temp pumps into cell training by the second peristaltic pump 1302
Support bag.
It is additionally provided with gas mixing units, the source of the gas outside gas mixing units connection in the inside of switch board 13, is mainly
Oxygen, air and carbon dioxide.Through gas vent 1305 after extraneous gas entrance gas mixing units is mixed, flow through the 3rd
Cell culture bags is entered after pipeline (not shown).Gas mixing units link control module 7, is controlled gas by control module 7
The uninterrupted of the supply of body, such as gas, the time of conveying and the component ratio etc. of various gas.
In the present embodiment, switch board is additionally provided with pH value detection tabs 1303 and dissolved oxygen detection tabs 1304, and all
Sensor connector in difference link control module 7 and cell culture bags, by the pH value recorded in cell culture bags and dissolved oxygen
The signal of amount passes to control module 7.PH detection tabs 1303 and dissolved oxygen detection tabs 1304 all use on market conventional
Signal transmission joint, for example with SMA905 plug.PH detection tabs 1303 and dissolved oxygen detection tabs 1304 are cultivated with cell
Signal conducting piece (not shown) is used to connect between Dai, such as light connecting line common on market.
Embodiment 5 control module
Seeing Figure 14, for further optimizing design scheme, present invention additionally comprises control module 7, control module 7 is arranged on
On computer, include but not limited to illumination component control unit；It is permissible that Moveable support connects control unit, such as user
Control stepper motor by inputting specific numerical value and then control the displacement of Moveable support 9；Check unit, mainly
For user check under current state by object lens it is observed that content and the parameters of cell growing environment；Storage
Memory cell, is mainly used in storing user and thinks that the environment in the content observed and cell growth process that need to preserve is joined
Number, such as pH value and dissolved oxygen etc., in case again checking；Gas control unit, is mainly used in controlling gas mixing units, when needing
Time to be taken a breath, extraneous gas is inputted after mixing cell culture bags；Nutrient solution control unit, Main Function is when cell is trained
When cell culture fluid in foster bag needs to change, outside cell culture fluid is heated, and inputs cell culture bags.
User can control whole system by control unit 7 and check and record various cell cultivate in each
Plant parameter and the structure etc. of cell.
Those skilled in the art all understand, and above-mentioned control module as above is for the control of Moveable support
Journey, the control process to illumination component, check the content of cell culture bags and the process of various parameter, control external air source with
And cell culture fluid enter cell culture bags process, all can utilize computer of the prior art, integrated circuit modules, can
Programmed logic device, other hardware or existing software module realize.
The principle of above-described embodiment only illustrative present invention and effect thereof, not for limiting the present invention.Any ripe
Above-described embodiment all can be modified under the spirit and the scope of the present invention or change by the personage knowing this technology.Cause
This, have usually intellectual such as complete with institute under technological thought without departing from disclosed spirit in art
All equivalences become are modified or change, and must be contained by the claim of the present invention.
Claims (27)
1. a full-automatic cell culture systems, it is characterised in that described cell culture system at least includes: control module, control
Platform processed, dark ground microscope, cell culture table, cell culture bags and the power module observed online for cell cultivation；
Described cell culture table includes that culture bag bracket, rocking carrier and agitating device, described culture bag bracket are provided with arcuate bottom
Plate and cell culture bags fixed component, described rocking carrier includes that swinging base, described swinging base are provided with support arm, described training
Supporting bag bracket and described rocking carrier to fix through support arm and be connected, described agitating device includes that pedestal, pedestal are provided with and waves assembly,
Described swinging base is connected with waving assembly, and described curved plate is provided with object lens and inserts breach；
Described cell culture bags, including closed bag, is provided with transparent observing district in the middle part of the bottom surface of described bag；Described bag is put
In cell culture table, described transparent observing district mates with object lens gap position；
The described dark ground microscope cultivating online observation for cell, including object lens, described object lens just can be inserted into cell training
Support the object lens on shaking table and insert breach；
Described control platform is connected to cell respectively and cultivates the online dark ground microscope observed and cell culture table；
Described control module connects control platform；
Described power module is that whole system is powered.
Full-automatic cell culture systems the most according to claim 1, it is characterised in that: described cultivation for cell is seen online
The dark ground microscope examined includes that illumination component, Moveable support, support base, photo-sensitive cell, caliber unit, A/D change
Unit, described illumination component is arranged on the top of Moveable support, and described Moveable support is arranged on support base, institute
Stating caliber unit and be connected to Moveable support bottom, described object lens are arranged on caliber unit and corresponding under illumination component
Side, described photo-sensitive cell connects sense for the light signal gathering on object lens, described A/D converting unit in being arranged on caliber unit
Optical element, described control module connects A/D converting unit.
Full-automatic cell culture systems the most according to claim 2, it is characterised in that: described illumination component includes circle
Lamp socket, and it is arranged on lamp socket the illuminating lamp surrounding several concentric arrays, the described concentrically ringed center of circle and the circle of lamp socket
Heart position consistency.
Full-automatic cell culture systems the most according to claim 3, it is characterised in that: the distance of described lamp socket to object lens is
10-30 centimetre.
Full-automatic cell culture systems the most according to claim 4, it is characterised in that: the light source of described illuminating lamp and object lens
Form dark field, meet the needs of dark field illumination.
Full-automatic cell culture systems the most according to claim 3, it is characterised in that: described illuminating lamp is LED.
Full-automatic cell culture systems the most according to claim 2, it is characterised in that: described support base includes stepping electricity
Machine, slide mechanism and base, described slide mechanism includes that slide block and slide rail, described control module connect and control stepper motor,
Described stepper motor connection sliding block, described slide block is slidably connected on base and horizontally moveable through slide rail, described packaged type
Support is arranged on slide block.
Full-automatic cell culture systems the most according to claim 1, it is characterised in that: arrange one on described curved plate
Or multiple accessory fixed hole position, leave the space for installing or insert outside appurtenances under described accessory fixed hole position.
Full-automatic cell culture systems the most according to claim 1, it is characterised in that: described curved plate is provided with heating
Plate.
Full-automatic cell culture systems the most according to claim 1, it is characterised in that: the edge of described curved plate sets
There is baffle plate.
11. full-automatic cell culture systems according to claim 1, it is characterised in that: described cell culture bags fixed part
Part is located at the both sides of curved plate, and including the platform extended from the lateral both sides of curved plate two, described platform is provided with hold-down bars
Fixture and/or hold-down bars interposer.
12. full-automatic cell culture systems according to claim 1, it is characterised in that: described swinging base is flat board, two
End be provided with support arm, culture bag bracket does not contacts with swinging base, between leave space with install or insertion outside appurtenances.
13. full-automatic cell culture systems according to claim 1, it is characterised in that wave assembly described in: and include hinged
Seat and at least one mechanism that pumps, described hinged seat is located on pedestal, and described swinging base is hinged with hinged seat, institute
State the mechanism that pumps be connected with swinging base or compress mutually.
14. full-automatic cell culture systems according to claim 1, it is characterised in that described cell culture bags includes: bag
The fixed component of body both sides, described closed upper face of bag body is provided with outside liquid adding mouth, outside liquid injection port, gas feed
And gas vent, described closed bag bottom surface is provided with liquids recovery mouth and at least one sensor connector, described outside liquid
It is equipped with aseptic snap joint on adding mouth, outside liquid injection port, gas feed, gas vent and liquids recovery mouth.
15. full-automatic cell culture systems according to claim 14, it is characterised in that: described closed bag is by upper bag
Sheet, lower bag sheet, left side bag webs and right side bag webs surround under a stereoscopic bag chamber, described left side bag webs and described right side bag webs jointly
Base is curved, and described left side bag webs and the described right side equal ovalize of bag webs, described upper bag sheet and lower bag sheet are rectangular.
16. full-automatic cell culture systems according to claim 14, it is characterised in that: described closed bag interior
Layer is polyethylene layer.
17. full-automatic cell culture systems according to claim 14, it is characterised in that: used by described closed bag
Material is five layers of composite construction, is followed successively by polyethylene layer, adhesive layer, ethylene, propylene alcohol layer, adhesive layer and polyethylene from the inside to the outside
Layer.
18. full-automatic cell culture systems according to claim 14, it is characterised in that: described sensor connector is provided with
One or more.
19. full-automatic cell culture systems according to claim 18, it is characterised in that: described sensor connector is non-
Touch sensor joint or touch sensor joint.
The 20. full-automatic cell culture systems stated according to claim 19, it is characterised in that: described contactless sensor connects
Head includes basal disc and sensor probe accommodating cavity, and described basal disc is provided with transparent partition, described sensor probe accommodating cavity and institute
Stating the side that basal disc is connected and is positioned at described transparent partition, the opposite side of described transparent partition is provided with conversion film.
21. full-automatic cell culture systems according to claim 20, it is characterised in that: described film of changing is into pH mutagens look
Film or dissolved oxygen cause color-changing membrane.
22. according to the full-automatic cell culture systems described in claim 1, it is characterised in that: described control platform includes control
Cabinet processed, and automatic heating unit, preheating bag and the peristaltic pump being arranged on switch board；Described automatic heating unit includes preheating
Plate, described preheating bag is arranged on preheating table, and described peristaltic pump includes the first peristaltic pump and the second peristaltic pump, and described cell preheats
The import of bag is by the cell culture fluid outside the first pipeline communication, and the outlet of described preheating bag connects cell by second pipe
Culture bag, described first peristaltic pump connects the first pipeline, and described second peristaltic pump connects second pipe, described automatic heating list
Unit, the first peristaltic pump and the second peristaltic pump link control module.
23. according to the full-automatic cell culture systems described in claim 22, it is characterised in that: also set inside described switch board
Having gas mixing units, the 3rd pipeline communication cell culture bags is passed through in the gas outlet of described gas mixing units, and described gas mixes
The air inlet closing unit connects external air source, described gas mixing units link control module.
24. according to the full-automatic cell culture systems described in claim 22, it is characterised in that: it is additionally provided with on described switch board
PH value detection tabs and dissolved oxygen detection tabs, described pH value detection probe and dissolved oxygen detection probe link control module are with thin
Born of the same parents' culture bag.
25. according to the full-automatic cell culture systems described in claim 1, it is characterised in that described control module includes:
Moveable support control unit, for controlling the movement of Moveable support；
Illumination component control unit, for controlling the switch of illumination component；
Check unit, for checking the content that under current state, object lens are observed, and cell growing environment under current state
Parameters；
Storage element, for storing the content observed needing to preserve and the parameters of record cell growing environment；
Gas control unit, for controlling the gas conveying in cell culture bags；
Cell culture fluid control unit, for controlling temperature and the supply of cell culture fluid.
26. according to the dark ground microscope cultivating online observation for cell described in claim 1-25 any one claim
For observation of cell culture apparatus.
27. are used for cultivating cell according to the cell culture bags described in claim 1-25 any one claim.
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| CN201610325576.4A CN105925481A (en) | 2016-05-16 | 2016-05-16 | Full-automatic cell continuous culture system |
| US16/064,414 US10934513B2 (en) | 2015-12-23 | 2016-12-15 | Fully automated continuous cell culture system |
| JP2018533724A JP6889723B2 (en) | 2015-12-23 | 2016-12-15 | Cell culture device |
| PCT/CN2016/110035 WO2017107837A1 (en) | 2015-12-23 | 2016-12-15 | Fully automated continuous cell culture system |
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| CN201610325576.4A CN105925481A (en) | 2016-05-16 | 2016-05-16 | Full-automatic cell continuous culture system |
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017107837A1 (en) * | 2015-12-23 | 2017-06-29 | 上海吉凯基因科技有限公司 | Fully automated continuous cell culture system |
| CN108004141A (en) * | 2017-12-27 | 2018-05-08 | 广州汉腾生物科技有限公司 | Rock reactor |
| CN108315259A (en) * | 2018-05-09 | 2018-07-24 | 武汉赛科成科技有限公司 | A kind of disposable film device of fluid bed cell culture of filling chip carrier |
| CN108795754A (en) * | 2018-04-23 | 2018-11-13 | 苏州欧飞纳米科技有限公司 | The control system and method for bioreactor culture parameter |
| CN110358684A (en) * | 2019-08-16 | 2019-10-22 | 世翱（上海）生物医药科技有限公司 | A kind of automatic culture apparatus of cell and its application method |
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| WO2020181709A1 (en) * | 2019-03-12 | 2020-09-17 | 华道(上海)生物医药有限公司 | Fully enclosed cell incubation system |
| CN112646693A (en) * | 2020-12-21 | 2021-04-13 | 上海东富龙医疗装备有限公司 | Swing type cell amplification culture system |
| WO2021114085A1 (en) * | 2019-12-10 | 2021-06-17 | 苏州生动细胞生物科技有限公司 | Fixable cell culture assembly |
| CN114051529A (en) * | 2019-06-30 | 2022-02-15 | 美国圣戈班性能塑料公司 | Cell culture system |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101048492A (en) * | 2004-11-09 | 2007-10-03 | 株式会社日立医药 | Cell cultivating device, image processing device and cell detecting system |
| CN101812405A (en) * | 2010-04-30 | 2010-08-25 | 惠倪 | Polygonal plastic bag swing cell reactor and method for culturing animal cells |
| CN102841080A (en) * | 2012-08-06 | 2012-12-26 | 上海交通大学 | Two-parameter optical fiber sensor used for measurement of pH value and dissolved oxygen |
| CN103207151A (en) * | 2013-04-18 | 2013-07-17 | 上海科源电子科技有限公司 | On-line cell microscopic observer for biological reactor |
| CN103361271A (en) * | 2013-07-19 | 2013-10-23 | 广州中玺医疗科技有限公司 | Cell proliferation bag and cell proliferation device |
| CN104946530A (en) * | 2015-05-07 | 2015-09-30 | 中国航天员科研训练中心 | Automatic passage type cell long-term experiment integrated module capable of being used for observing on line in real time |
| CN206014938U (en) * | 2016-05-16 | 2017-03-15 | 上海吉凯基因科技有限公司 | Full-automatic cell continuous culture system |
-
2016
- 2016-05-16 CN CN201610325576.4A patent/CN105925481A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101048492A (en) * | 2004-11-09 | 2007-10-03 | 株式会社日立医药 | Cell cultivating device, image processing device and cell detecting system |
| CN101812405A (en) * | 2010-04-30 | 2010-08-25 | 惠倪 | Polygonal plastic bag swing cell reactor and method for culturing animal cells |
| CN102841080A (en) * | 2012-08-06 | 2012-12-26 | 上海交通大学 | Two-parameter optical fiber sensor used for measurement of pH value and dissolved oxygen |
| CN103207151A (en) * | 2013-04-18 | 2013-07-17 | 上海科源电子科技有限公司 | On-line cell microscopic observer for biological reactor |
| CN103361271A (en) * | 2013-07-19 | 2013-10-23 | 广州中玺医疗科技有限公司 | Cell proliferation bag and cell proliferation device |
| CN104946530A (en) * | 2015-05-07 | 2015-09-30 | 中国航天员科研训练中心 | Automatic passage type cell long-term experiment integrated module capable of being used for observing on line in real time |
| CN206014938U (en) * | 2016-05-16 | 2017-03-15 | 上海吉凯基因科技有限公司 | Full-automatic cell continuous culture system |
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10934513B2 (en) | 2015-12-23 | 2021-03-02 | Shanghai GenBase Biotechnology Co., Ltd. | Fully automated continuous cell culture system |
| WO2017107837A1 (en) * | 2015-12-23 | 2017-06-29 | 上海吉凯基因科技有限公司 | Fully automated continuous cell culture system |
| CN108004141A (en) * | 2017-12-27 | 2018-05-08 | 广州汉腾生物科技有限公司 | Rock reactor |
| CN108795754A (en) * | 2018-04-23 | 2018-11-13 | 苏州欧飞纳米科技有限公司 | The control system and method for bioreactor culture parameter |
| CN108315259A (en) * | 2018-05-09 | 2018-07-24 | 武汉赛科成科技有限公司 | A kind of disposable film device of fluid bed cell culture of filling chip carrier |
| WO2019214465A1 (en) * | 2018-05-09 | 2019-11-14 | 武汉赛科成科技有限公司 | Fluidized bed cell culture disposable membrane device filled with flaky carriers |
| CN108315259B (en) * | 2018-05-09 | 2024-01-23 | 武汉赛科成科技有限公司 | Fluidized bed cell culture disposable membrane device filled with sheet-shaped carrier |
| WO2019219050A1 (en) * | 2018-05-18 | 2019-11-21 | Huacells Corporation | Automated cell culturing |
| TWI765154B (en) * | 2018-05-18 | 2022-05-21 | 美商華賽公司 | Automative cell culturing system and method for culturing cells |
| WO2020181709A1 (en) * | 2019-03-12 | 2020-09-17 | 华道(上海)生物医药有限公司 | Fully enclosed cell incubation system |
| US11959056B2 (en) | 2019-06-30 | 2024-04-16 | Saint-Gobain Performance Plastics Corporation | Cell culture system |
| CN114051529A (en) * | 2019-06-30 | 2022-02-15 | 美国圣戈班性能塑料公司 | Cell culture system |
| CN110358684A (en) * | 2019-08-16 | 2019-10-22 | 世翱（上海）生物医药科技有限公司 | A kind of automatic culture apparatus of cell and its application method |
| CN110938543A (en) * | 2019-11-26 | 2020-03-31 | 浙江大学 | Bioreactor for cell and tissue culture |
| WO2021114085A1 (en) * | 2019-12-10 | 2021-06-17 | 苏州生动细胞生物科技有限公司 | Fixable cell culture assembly |
| CN111197006B (en) * | 2020-01-16 | 2023-09-12 | 杭州键一生物科技有限公司 | CAR-T cell expander |
| CN111197006A (en) * | 2020-01-16 | 2020-05-26 | 杭州键一生物科技有限公司 | CAR-T cell expander |
| CN112646693A (en) * | 2020-12-21 | 2021-04-13 | 上海东富龙医疗装备有限公司 | Swing type cell amplification culture system |
| WO2022134453A1 (en) * | 2020-12-23 | 2022-06-30 | 基亚生物科技股份有限公司 | Automated cell culture device |
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