CN109055217A - high-throughput three-dimensional cell culture system - Google Patents
high-throughput three-dimensional cell culture system Download PDFInfo
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- CN109055217A CN109055217A CN201811105819.9A CN201811105819A CN109055217A CN 109055217 A CN109055217 A CN 109055217A CN 201811105819 A CN201811105819 A CN 201811105819A CN 109055217 A CN109055217 A CN 109055217A
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- 238000004113 cell culture Methods 0.000 title claims abstract description 38
- 239000007788 liquid Substances 0.000 claims abstract description 18
- 230000002380 cytological effect Effects 0.000 claims abstract description 17
- 238000011160 research Methods 0.000 abstract description 10
- 210000004027 cell Anatomy 0.000 abstract description 8
- 206010028980 Neoplasm Diseases 0.000 abstract description 3
- 210000000130 stem cell Anatomy 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 12
- 238000005516 engineering process Methods 0.000 description 6
- 238000010586 diagram Methods 0.000 description 5
- 239000000017 hydrogel Substances 0.000 description 5
- 239000012620 biological material Substances 0.000 description 4
- 230000010355 oscillation Effects 0.000 description 3
- 238000000889 atomisation Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
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- 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
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- 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
- C12M23/16—Microfluidic devices; Capillary tubes
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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
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/14—Scaffolds; Matrices
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Abstract
The invention discloses a kind of high-throughput Three-dimensional cell culture systems, comprising: the viscous body allocation component of multifunction manipulator platform, automatic cytological incubator, rotating mechanical arm, the first mechanical gripper, first mechanical arm, Multi-channel liquid allocation component, multichannel, second mechanical arm, the second mechanical gripper, high-throughput microlayer model gel forming component.High-throughput Three-dimensional cell culture system of the invention can realize the accurate distribution of liquid and viscous body by Multi-channel liquid allocation component and the viscous body allocation component of multichannel with high throughput；The crawl of porous plate culture plate is realized by the first mechanical gripper, the second mechanical gripper, rotating mechanical arm, shifts, uncap, the quiet runs such as lid lid, to realize automatic cytological dimensional culture.High-throughput Three-dimensional cell culture system of the invention is safe and reliable, efficiently convenient, each area research personnel such as can meet high-flux medicaments sifting, stem-cell research and tumor research high-flux cell three dimensional culture system.
Description
Technical field
The present invention relates to cell biology, organizational project and biomaterial and field of biotechnology, in particular to a kind of.
Background technique
It is known that three-dimensional cell cultivation technology is relative to traditional two dimension culture, there is many advantages, researchers
This conclusion is all confirmed from metabolism group, protein expression, nucleic acid level, but raw in organizational project, biomaterial and cell
The field of biotechnology such as object are often used the dimensional culture technology of cell, and biological study personnel are often due to lacking biological material
Expect that the knowledge of aspect is still studied using traditional two-dimentional cell culture model, or by means of letters such as hydrogels in the market
Single Three-dimensional cell culture product carries out, and not only expensive there is also many drawbacks.Common three-dimensional cell cultivation technology is pressed
According to whether there is or not brackets to be divided into no support rack type three-dimensional cell cultivation and support rack type three-dimensional cell cultivation, no bracket three-dimensional cell cultivation is divided into
Ultralow adhesion sheet culture, Hanging drop culture, rotary rolling culture and magnetization cultivation, and support rack type three-dimensional cell cultivation is according to bracket
The difference of type is divided into nano-screen three-dimensional cell cultivation and hydrogel three-dimensional cell cultivation.
Three-dimensional cell cultivation has extremely wide answer in stem-cell research, tumor research and drug discovery and development field
With prospect, as needed largely to test in drug screening research, the less dimensional culture of the dimensional culture of simplified manual and channel
Mode is increasingly unable to satisfy application demand, and three-dimensional cell cultivation technology is many kinds of, and wherein culture effect is best for water-setting
The dimensional culture technology of glue form, but due to the larger never automation solutions of automation difficulty degree, and automate
The lesser drop culture of difficulty and nano-screen Three-dimensional cell culture method automation solutions are applied more.Therefore have
Necessity researches and develops a kind of high-flux cell three dimensional culture system for being directed to form of hydrogels dimensional culture technology.
Summary of the invention
In view of the above-mentioned deficiencies in the prior art, the technical problem to be solved by the present invention is that providing a kind of high-throughput three
Tie up cell culture system.
In order to solve the above technical problems, the technical solution adopted by the present invention is that: a kind of high throughput Three-dimensional cell culture system,
Include:
Multifunction manipulator platform；
Automatic cytological incubator is provided with rotating mechanical arm moving up and down, sets on the rotating mechanical arm
It is equipped with the first mechanical gripper；
First mechanical arm is arranged on the multifunction manipulator platform, can be on the multifunction manipulator platform
It is moved along Y-axis；Multi-channel liquid allocation component and multichannel are provided with by the first multifunction module in the first mechanical arm
Viscous body allocation component, first multifunction module is for driving the Multi-channel liquid allocation component and the viscous body of multichannel
Allocation component is inside and outside moved along X-axis in the first mechanical arm and is moved up and down along Z axis；
Second mechanical arm is arranged on the multifunction manipulator platform, can be on the multifunction manipulator platform
It is moved along Y-axis；The second mechanical gripper and high-throughput microlayer model are provided with by the second multifunction module in the second mechanical arm
Gel forming component, second multifunction module is for driving second mechanical gripper and high-throughput microlayer model gel forming
Component is inside and outside moved along X-axis in the second mechanical arm and is moved up and down along Z axis.
Preferably, it is provided on the bottom plate of the multifunction manipulator platform multiple for fixing consolidating for porous culture plate
Fixed rack.
Preferably, the automatic cytological incubator is arranged in the multifunction manipulator platform sides, is arranged inside
There is porous culture plate swivel mount.
Preferably, it is provided on the porous culture plate swivel mount multiple for fixing the culture branch of porous culture plate
Frame.
Preferably, porous culture plate swivel mount bottom is provided with motor.
Preferably, the outside of the automatic cytological incubator, the rotating machinery is arranged in the rotating mechanical arm
The carrying of arm and the first mechanical gripper for realizing porous culture plate between the fixed bracket and culture bracket.
Preferably, viscous body distribution pipette tips are provided in the viscous body allocation component of the multichannel.
Preferably, first mechanical gripper and the first mechanical gripper structure are identical, include drive module and setting
Gripper in the drive module bottom.
Preferably, the gripper includes the grasping plate of 4 pieces of L-types, and the drive module is for driving the grasping plate driving
The sliding in module bottom progress back and forth or left and right direction.
The beneficial effects of the present invention are: high-throughput Three-dimensional cell culture system of the invention, is distributed by Multi-channel liquid
Component and the viscous body allocation component of multichannel can realize the accurate distribution of liquid and viscous body with high throughput；Pass through high-throughput micro- liquid
Gel cross-linkage agent is generated microlayer model by high frequency oscillation mode and carries out gel cross-linkage by drop gel forming component；Pass through the first machinery
Handgrip, the second mechanical gripper, rotating mechanical arm realize the crawl of porous plate culture plate, shift, uncap, the steady behaviour such as lid lid
Make, to realize automatic cytological dimensional culture.High-throughput Three-dimensional cell culture system of the invention is safe and reliable, efficiently just
Prompt, each area research personnel such as can meet high-flux medicaments sifting, stem-cell research and tumor research high-flux cells are three-dimensional
Culture systems.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of high-throughput Three-dimensional cell culture system of the invention；
Fig. 2 is the structural schematic diagram of multifunction manipulator platform of the invention；
Fig. 3 is the structural schematic diagram of automatic cytological incubator of the invention；
Fig. 4 is the structural schematic diagram of the first mechanical gripper of the invention, the second mechanical gripper；
Fig. 5 is the structural schematic diagram of Multi-channel liquid allocation component of the invention.
Description of symbols:
01 first mechanical arm；02 syringe pump；03 Multi-channel liquid allocation component；The viscous body allocation component of 04 multichannel；05
Porous cell culture plate；06 automatic cytological incubator；07 second mechanical arm；08 culture bracket；09 high-throughput microlayer model gel
Molding assembly；10 second mechanical grippers；11 power switches；12 porous culture plate swivel mounts；13 rotating mechanical arms；14 motors；15
First mechanical gripper；16 first multifunction modules；17 second multifunction modules；18 fixed brackets；20 multifunction manipulator platforms；
30 drive modules；31 grasping plates；40 viscous bodies distribute pipette tips；32 dispensing heads；33 distribution pipes.
Specific embodiment
The present invention will be further described in detail below with reference to the embodiments, to enable those skilled in the art referring to specification
Text can be implemented accordingly.
It should be appreciated that such as " having ", "comprising" and " comprising " term used herein are not precluded one or more
The presence or addition of a other elements or combinations thereof.
As shown in Figs. 1-5, a kind of high-throughput Three-dimensional cell culture system of the present embodiment, comprising:
Multifunction manipulator platform 20；
Automatic cytological incubator 06, is provided with rotating mechanical arm 13 moving up and down, on rotating mechanical arm 13
It is provided with the first mechanical gripper 15, rotating mechanical arm 13 can be moved freely up and down, to cooperate the first mechanical gripper 15 to facilitate realization
The carrying of porous cell culture plate 05；Porous cell is carried out using porous culture plate swivel mount 12 in automatic cytological incubator 06
The placement and cell culture of culture plate 05, cooperative mechanical handgrip realize the automation culture of cell；And rotating mechanical arm 13 is arranged
In the outside of the automatic cytological incubator 06, can smoothly be closed with the hermatic door guaranteed on automatic cytological incubator 06；
First mechanical arm 01 is arranged on multifunction manipulator platform 20, can be on multifunction manipulator platform 20 along Y
Axis movement；Multi-channel liquid allocation component 03 is provided with by the first multifunction module 16 in first mechanical arm 01 and multichannel is viscous
Stagnant body allocation component 04, the first multifunction module 16 is for driving Multi-channel liquid allocation component 03 and the viscous body distribution of multichannel
Component 04 is inside and outside moved along X-axis in first mechanical arm 01 and is moved up and down along Z axis；
Second mechanical arm 07 is arranged on multifunction manipulator platform 20, can be on multifunction manipulator platform 20 along Y
Axis movement；Second mechanical gripper 10 is provided with by the second multifunction module 17 in second mechanical arm 07 and high-throughput microlayer model is solidifying
Gum forming component 09, the second multifunction module 17 is for driving the second mechanical gripper 10 and high-throughput microlayer model gel forming component
09 inside and outside moves along X-axis in second mechanical arm 07 and moves up and down along Z axis.
Wherein, it is provided on the bottom plate of multifunction manipulator platform 20 multiple disposed in parallel for fixing porous culture plate
Fixation bracket 18.Multiple porous culture plates can be placed simultaneously and are operated, and porous cell culture includes 6 orifice plates, 12 holes
Plate, 24 orifice plates, 96 orifice plates, 384 orifice plates etc..
Wherein, automatic cytological incubator 06 is arranged in 20 side of multifunction manipulator platform, and porous training is arranged inside
Support plate swivel mount 12.It is provided on porous culture plate swivel mount 12 multiple for fixing the culture bracket 08 of porous culture plate.It is more
12 bottom of well culture plate swivel mount is provided with motor 14, and motor 14 drives porous culture plate swivel mount 12 to rotate.Rotating mechanical arm
13 and first mechanical gripper 15 for realizing porous culture plate in fixed bracket 18 and cultivate the carrying between bracket 08, the first machine
Tool handgrip 15 and the second mechanical gripper 10 are also able to achieve the crawl of porous plate culture plate, shift, uncap, the quiet runs such as lid lid,
To realize automatic cytological dimensional culture.
Wherein, Multi-channel liquid allocation component 03 and the viscous body allocation component 04 of multichannel can realize with high throughput liquid and
The accurate distribution of viscous body.Multi-channel liquid allocation component 03 includes dispensing head 32 and is connected to more points of 32 lower end of dispensing head
33 are piped, viscous body distribution pipette tips 40 are provided in the viscous body allocation component 04 of multichannel.Viscous body distribution Special gun head includes
Piston, it can be achieved that viscous body accurate distribution.
Wherein, the first mechanical gripper 15 is identical with 10 structure of the second mechanical gripper, includes that drive module 30 and setting exist
The gripper of 30 bottom of drive module.Gripper includes the grasping plate 31 of 4 pieces of L-types, and drive module 30 is for driving grasping plate 31 in driving mould
The sliding in 30 bottom of block progress back and forth or left and right direction.
Wherein, syringe pump 02 is additionally provided on multifunction manipulator platform 20, the side of multifunction manipulator platform 20 is set
It is equipped with power switch 11.
Wherein, each function such as first mechanical arm 01, second mechanical arm 07, the first mechanical gripper 15, second mechanical gripper 10
Energy module can be controlled by computer.
Wherein, gel cross-linkage agent is generated microlayer model by high frequency oscillation mode by high-throughput microlayer model gel forming component 09
Carry out gel cross-linkage.High-throughput microlayer model gel forming component 09 can carry out microlayer model hair according to porous culture plate type difference
Generating apparatus conversion carries out high-throughput water-setting gum forming to match different types of tissue culture plate, use high frequency oscillation or its
His atomization means make crosslinking agent be atomized to form the cross moulding that micron order droplet carries out biomaterial.Microlayer model hair therein
Generating apparatus uses modular Machine Design, can be converted by disassembly, interior design has microchannel to guarantee each porous plate
The corresponding generation outlet atomization situation of culture hole is identical.
When work, porous culture plate is placed on the fixation bracket 18 on 20 lower section bottom plate of multifunction manipulator platform, is made
Operation of uncapping is carried out with the second mechanical gripper 10, the hydrogel and cell suspension of pre-configuration pass through the viscous body distribution group of multichannel
Part 04 is added in the porous culture plate uncapped, then is atomized crosslinking agent to be formed by high-throughput microlayer model gel forming component 09
Microlayer model carries out the crosslinking of hydrogel, after a period of time gel-forming, Multi-channel liquid allocation component 03 is utilized to add culture medium
To porous culture plate, the second mechanical gripper 10 completes lid lid operation, and will be more by rotating mechanical arm 13 and the first mechanical gripping
Porocyte culture plates 05 are transferred to porous culture plate swivel mount 12, and porous cell culture plate 05 is placed on designated position and is carried out carefully
The dimensional culture of born of the same parents.
Although the embodiments of the present invention have been disclosed as above, but its is not only in the description and the implementation listed
With it can be fully applied to various fields suitable for the present invention, for those skilled in the art, can be easily
Realize other modification, therefore without departing from the general concept defined in the claims and the equivalent scope, the present invention is simultaneously unlimited
In specific details.
Claims (9)
1. a kind of high throughput Three-dimensional cell culture system characterized by comprising
Multifunction manipulator platform；
Automatic cytological incubator is provided with rotating mechanical arm moving up and down, is provided on the rotating mechanical arm
First mechanical gripper；
First mechanical arm is arranged on the multifunction manipulator platform, can be on the multifunction manipulator platform along Y-axis
Movement；Multi-channel liquid allocation component and the viscous body of multichannel are provided with by the first multifunction module in the first mechanical arm
Allocation component, first multifunction module is for driving the Multi-channel liquid allocation component and the viscous body distribution group of multichannel
Part is inside and outside moved along X-axis in the first mechanical arm and is moved up and down along Z axis；
Second mechanical arm is arranged on the multifunction manipulator platform, can be on the multifunction manipulator platform along Y-axis
Movement；In the second mechanical arm by the second multifunction module be provided with the second mechanical gripper and high-throughput microlayer model gel at
Type component, second multifunction module is for driving second mechanical gripper and high-throughput microlayer model gel forming component to exist
It inside and outside moves in the second mechanical arm along X-axis and moves up and down along Z axis.
2. high throughput Three-dimensional cell culture system according to claim 1, which is characterized in that the multifunction manipulator is flat
It is provided on the bottom plate of platform multiple for fixing the fixation bracket of porous culture plate.
3. high throughput Three-dimensional cell culture system according to claim 2, which is characterized in that the automatic cytological culture
Case is arranged in the multifunction manipulator platform sides, and porous culture plate swivel mount is arranged inside.
4. high throughput Three-dimensional cell culture system according to claim 3, which is characterized in that the porous culture plate rotation
It is provided on frame multiple for fixing the culture bracket of porous culture plate.
5. high throughput Three-dimensional cell culture system according to claim 4, which is characterized in that the porous culture plate rotation
Frame bottom is provided with motor.
6. high throughput Three-dimensional cell culture system according to claim 5, which is characterized in that the rotating mechanical arm setting
In the outside of the automatic cytological incubator, the rotating mechanical arm and the first mechanical gripper exist for realizing porous culture plate
Carrying between the fixed bracket and culture bracket.
7. high throughput Three-dimensional cell culture system according to claim 1, which is characterized in that the viscous body of multichannel point
Viscous body distribution pipette tips are provided in distribution assembly.
8. high throughput Three-dimensional cell culture system according to claim 1, which is characterized in that first mechanical gripper and
First mechanical gripper structure is identical, includes drive module and the gripper that the drive module bottom is arranged in.
9. high throughput Three-dimensional cell culture system according to claim 8, which is characterized in that the gripper includes 4 pieces of L-types
Grasping plate, the drive module be used for drive the grasping plate drive module bottom carry out back and forth or left and right direction sliding.
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| CN201811105819.9A CN109055217B (en) | 2018-09-21 | 2018-09-21 | High-throughput three-dimensional cell culture system |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110093250A (en) * | 2019-05-14 | 2019-08-06 | 滕文友 | A kind of full-automatic Culture Mycoplasma sample-adding detector and its culture sample-adding detection method |
| CN111948968A (en) * | 2020-08-16 | 2020-11-17 | 天津智橙物联科技有限公司 | High-throughput micro-reaction cell culture flexible automatic control system and method |
| CN118222399A (en) * | 2024-05-24 | 2024-06-21 | 华清智美(深圳)生物科技有限公司 | Culture device and culture method |
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| CN102174395A (en) * | 2011-01-30 | 2011-09-07 | 中国科学院广州生物医药与健康研究院 | Automation augmentation and culture system of induced pluripotent stem cells |
| US20130210130A1 (en) * | 2010-04-21 | 2013-08-15 | Octane Biotech, Inc. | Automated cell culture system |
| CN104403923A (en) * | 2014-11-11 | 2015-03-11 | 南京卡迪奥密生物技术有限公司 | Three dimensional tissue and organ culture model, high throughput automatic stereo image analyzing platform and applications thereof |
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2018
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20130210130A1 (en) * | 2010-04-21 | 2013-08-15 | Octane Biotech, Inc. | Automated cell culture system |
| CN102174395A (en) * | 2011-01-30 | 2011-09-07 | 中国科学院广州生物医药与健康研究院 | Automation augmentation and culture system of induced pluripotent stem cells |
| CN104403923A (en) * | 2014-11-11 | 2015-03-11 | 南京卡迪奥密生物技术有限公司 | Three dimensional tissue and organ culture model, high throughput automatic stereo image analyzing platform and applications thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110093250A (en) * | 2019-05-14 | 2019-08-06 | 滕文友 | A kind of full-automatic Culture Mycoplasma sample-adding detector and its culture sample-adding detection method |
| CN111948968A (en) * | 2020-08-16 | 2020-11-17 | 天津智橙物联科技有限公司 | High-throughput micro-reaction cell culture flexible automatic control system and method |
| CN118222399A (en) * | 2024-05-24 | 2024-06-21 | 华清智美(深圳)生物科技有限公司 | Culture device and culture method |
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