CN108300660A - A kind of self-loopa organ chip dynamic cultivation device of cardiac muscle cell's Micropump driving - Google Patents
A kind of self-loopa organ chip dynamic cultivation device of cardiac muscle cell's Micropump driving Download PDFInfo
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- CN108300660A CN108300660A CN201810129812.4A CN201810129812A CN108300660A CN 108300660 A CN108300660 A CN 108300660A CN 201810129812 A CN201810129812 A CN 201810129812A CN 108300660 A CN108300660 A CN 108300660A
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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
- C12M21/00—Bioreactors or fermenters specially adapted for specific uses
- C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
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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
- C12M23/16—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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
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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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/18—External loop; Means for reintroduction of fermented biomass or liquid percolate
Abstract
A kind of self-loopa organ chip dynamic cultivation device of cardiac muscle cell's Micropump driving, including the lower layer chip of lamination successively from bottom to top, intermediate film and upper layer chip, upper layer chip includes cardiac muscle cell's Micropump module, lower layer chip includes self-circulation system module and organ chip culture module, self-circulation system module is interconnected with organ chip culture module, cardiac muscle cell's Micropump module is for simulating heart pumping blood function, self-circulation system module is for simulating blood of human body flow cycle, organ chip culture module is for simulating human organ function, the up-down vibration of intermediate film is driven by the autonomous beating of the cardiac muscle cell grown in cardiac muscle cell's Micropump module, realize that culture solution self-loopa in self-circulation system module is flowed, nutrient dynamics supply to organ chip culture module.The self-loopa organ chip dynamic cultivation device is supplied without external energy, closer to simulation of human body environment, and reduces volume.
Description
Technical field
The present invention relates to microfluidic chip technology, especially a kind of self-loopa organ chip of cardiac muscle cell's Micropump driving is dynamic
State culture apparatus and preparation method thereof.
Background technology
Organ chip be it is a kind of utilize microflow control technique, the master that can simulate human organ is produced on micro-fluidic chip
Want the bionic system of function.It not only has the characteristics that microflow control technique is miniaturized, is integrated, low consumed, while can be with structure
Build cell graphically cultivate, tissue-organizational interface and organ-organ interaction etc., to simulate the complicated knot of human organ
Structure, microenvironment and physiologic function.By fast development in recent years, researcher realizes on micro-fluidic chip
The structure of numerous human organs, such as chip liver, chip lung, chip intestines, chip kidney, chip blood vessel, chip heart and multiple organ
Chip etc..
Micropump be in microfluidic system realize microfluid accurately drive indispensable core component, be it is micro even more
The specific implementation form of small size micro fluid dynamcis technology.Micropump is defeated in biochemical analysis, microfluid (buffer solution, drug etc.)
The fields such as fortune, microelectronic chip cooling have a wide range of applications, and development has become the weight for weighing microfluidic system development level
Indicate.
The Micropump used in organ chip includes mainly piezoelectric micropump, electromagnetism Micropump, Pneumatic Micropump, electric heating Micropump at present
Etc., but these Micropumps all have the characteristics that one it is common, that is, the energy for being required for the external input energy, and being inputted
Source, such as electricity, thermal and magnetic etc. all more or less can generate a degree of influence to the cell in organ chip.Organ chip is
The micro-fluidic chip of human organ function is simulated, in human body, the nutrition supply of human organ is relaxed by the contraction of heart
Open what pumping obtained, so the use of cardiac muscle cell's pump being the bionics feature that organ chip pumps liquor charging body extremely meets human body.
The research of cardiac muscle cell's pump, foreign study personnel have been achieved for part achievement in research：2006, Tanaka et al.
It attempts to make one layer of cardiac muscular tissue using cardiac muscle cell, is layered on the surface of a pump housing, passes through the contraction compression chamber of cardiac muscle cell
Chamber interior volume controls the one-way flow that flow direction realizes liquid using lower side check valve.The shortcomings that this cardiac muscle cell's Micropump, is
Complicated, being one has the driving of valve Micropump, and resistance is relatively large, is unfavorable for cardiac muscle cell and drives liquid flowing.2007,
Be coated on a degradable spherical structures using cardiac muscle cell has been made a spherical cardiac muscle cell to Tanaka et al. again
Pump, cardiac muscle cell's pump of this shape can make full use of the convergent force of cardiac muscle cell, to generate larger pumping force, but he
And the one-way flow that this myocardium ball pump realizes liquid is not used, only realize driving liquid vibration.
Invention content
It is a primary object of the present invention in view of the deficiencies of the prior art, provide a kind of following certainly for cardiac muscle cell's Micropump driving
Ring organ chip dynamic cultivation device is supplied without external energy, closer to simulation of human body environment, and reduces volume.
To achieve the above object, the present invention uses following technical scheme：
A kind of self-loopa organ chip dynamic cultivation device of cardiac muscle cell's Micropump driving, including lamination successively from bottom to top
Lower layer chip, intermediate film and upper layer chip, the upper layer chip includes cardiac muscle cell's Micropump module, the lower layer chip packet
Include self-circulation system module and organ chip culture module, the self-circulation system module and the organ chip culture module phase
Intercommunicated, cardiac muscle cell's Micropump module is used for mould for simulating heart pumping blood function, the self-circulation system module
Anthropomorphic body blood circulation circuit, the organ chip culture module pass through the cardiac muscle cell for simulating human organ function
Power resources of the autonomous beating of the cardiac muscle cell grown in Micropump module as the pump housing, drive the upper and lower of the intermediate film to shake
It is dynamic, realize that culture solution in the self-circulation system mould unidirectional self-loopa flowing in the block, is trained the organ chip to realize
Support the nutrient dynamics supply of module.
Further：
Cardiac muscle cell's Micropump module includes Myocyte growth unit and culture solution feed unit, the cardiac muscle cell
Growing element provides growing environment for the growth of cardiac muscle cell, and the culture solution feed unit provides battalion for the growth of cardiac muscle cell
Support substance supply.
Be provided between cardiac muscle cell's Micropump mould Myocyte growth unit in the block and culture solution feed unit by
The fluid isolation structure that multiple isosceles trapezoids are lined up, the fluid isolation structure prevent celliferous extracellular matrix and culture medium
Between be mutually mixed, but do not influence to carry out mass exchange between celliferous extracellular matrix and culture medium；Preferably, described etc.
The trapezoidal upper bottom of waist, bottom and 10 ± 2 μm, 20 ± 5 μm and 10 ± 2 μm a height of.
The organ chip culture module includes organ chip growing element and culture solution feed unit, the organ chip
Growing element provides growing environment for the growth of cell in organ chip, and the culture solution feed unit is cell in organ chip
Growth provide nutriment supply.
Be provided between organ chip culture mould organ chip growing element in the block and culture solution feed unit by
The fluid isolation structure that multiple isosceles trapezoids are lined up, the fluid isolation structure prevent celliferous extracellular matrix and culture medium
Between be mutually mixed, but do not influence to carry out mass exchange between celliferous extracellular matrix and culture medium；Preferably, described etc.
The trapezoidal upper bottom of waist, bottom and 10 ± 2 μm, 20 ± 5 μm and 10 ± 2 μm a height of.
It is provided between the self-circulation system module and the organ chip culture module and is lined up by multiple isosceles trapezoids
Fluid isolation structure, the fluid isolation structure prevents to be mutually mixed between celliferous extracellular matrix and culture medium, but
It does not influence to carry out mass exchange between celliferous extracellular matrix and culture medium；Preferably, the upper bottom of the isosceles trapezoid, under
Bottom and 10 ± 2 μm, 20 ± 5 μm and 10 ± 2 μm a height of.
The materials'use PDMS of the lower layer chip, the intermediate film and the upper layer chip；Preferably, the centre
The thickness of film is in 250 μm of ± 100 μ ms；Preferably, three-decker is assembled by way of oxygen plasma treatment bonding, excellent
Selection of land, the time of oxygen plasma treatment is in the range of 30s ± 10s.
The extracellular matrix containing cardiac muscle cell is injected in cardiac muscle cell's Micropump mould Myocyte growth unit in the block,
Used cardiac muscle cell is selected from people source cardiac muscle cell, mouse cardiac myocytes and rat myocardial cell, used extracellular base
Matter is selected from rat-tail I-type collagen, fibrin, pigskin I-type collagen；Cardiac muscle cell's Micropump mould culture solution in the block
The basal medium containing growth factor is injected in supplying module, used basal medium is selected from DMEM culture mediums, DMEM/
F12 culture solutions, L-15 culture mediums；The organ structure that the organ chip culture module is simulated is selected from chip liver, chip lung, core
Piece kidney, chip intestines.
The self-circulation system module includes that self-loopa runner and setting maintain liquid unidirectional on the self-loopa runner
At least one check valve of flowing；Preferably, the check valve includes convergent divergent channel structure, the structure of the convergent divergent channel
Approximate isosceles trapezoid；Preferably, the bottom of the isosceles trapezoid is 0.6 ± 0.1mm, upper bottom is 0.2 ± 0.05mm, a height of 2.3
±0.2mm。
The self-circulation system module includes the pump head chamber being arranged in the self-loopa runner, the intermediate film
Up-down vibration compresses the volume of the pump head chamber, realizes the self-loopa stream in culture solution self-loopa runner described in culture solution
It is dynamic；Preferably, shrinkage expansion there are one being respectively set on the input side of the pump head chamber and the self-loopa runner of outlet side
Pipe structure, the structure proximate isosceles trapezoid of the convergent divergent channel.
The present invention has the advantages that：
The present invention provides a kind of self-loopa organ chip dynamic cultivation device of cardiac muscle cell's Micropump driving, is mainly used for profit
It with the autonomous beating characteristic of cardiac muscle cell, is flowed as power source drive liquid self circulation, is the growth of cell in organ chip
Dynamic culture environment and nutrition supply are provided, realize that heart self-loopa is the bionics system that human organ pumps nutriment
Structure.The present invention thoroughly solves the problems, such as that Micropump driving needs external energy supply in existing organ chip so that organ chip structure
The physiological environment closer to human body is made, using the autonomous beating ability of cardiac muscle cell, the unidirectional self-loopa of liquid is driven to flow.By
In not needing external energy supply, small closer to simulation of human body environment, the present invention has significant compared with the existing technology
Advantage.
Description of the drawings
Fig. 1 is the self-loopa organ chip dynamic cultivation device that cardiac muscle cell's Micropump of an embodiment of the present invention drives
Structural schematic diagram.
Fig. 2 is the self-loopa organ chip dynamic cultivation device that cardiac muscle cell's Micropump of an embodiment of the present invention drives
Perspective exploded view.
Fig. 3 is cardiac muscle cell's Micropump module diagram in an embodiment of the present invention.
Fig. 4 is the self-circulation system module diagram in an embodiment of the present invention.
Fig. 5 is the liver chip culture module diagram in an embodiment of the present invention.
Specific implementation mode
It elaborates below to embodiments of the present invention.It is emphasized that following the description is only exemplary,
The range being not intended to be limiting of the invention and its application.
Refering to fig. 1 to Fig. 2, in one embodiment, a kind of self-loopa organ chip dynamic of cardiac muscle cell's Micropump driving
Culture apparatus, including the lower layer chip 6, intermediate film 5 and upper layer chip 4 of lamination, the upper layer chip 4 wrap successively from bottom to top
Cardiac muscle cell's Micropump module 1 is included, the lower layer chip 6 includes self-circulation system module 2 and organ chip culture module 3, such as
But it is not limited to liver chip culture module, the self-circulation system module 2 is interconnected with the organ chip culture module 3, institute
It states cardiac muscle cell's Micropump module 1 and pumps blood function for simulating heart, the self-circulation system module 2 is for simulating human body blood
Liquid flow cycle, the organ chip culture module 3 pass through cardiac muscle cell's Micropump module for simulating human organ function
Power resources of the autonomous beating of the cardiac muscle cell grown in 1 as the pump housing, drive the up-down vibration of the intermediate film 5, real
Unidirectional self-loopa flowing of the existing culture solution in the self-circulation system module 2, to realize to the organ chip culture mould
The nutrient dynamics of block 3 supply.
Refering to Fig. 3, in a preferred embodiment, cardiac muscle cell's Micropump module 1 includes Myocyte growth unit 9 and the heart
Myocyte's culture solution feed unit 10, the Myocyte growth unit 9 provides growing environment for the growth of cardiac muscle cell, described
Myocardial cells culture liquid feed unit 10 provides nutriment supply for the growth of cardiac muscle cell.
Refering to Fig. 3, in a preferred embodiment, Myocyte growth unit 9 and the heart in cardiac muscle cell's Micropump module 1
Be provided with the fluid isolation structure 11 lined up by multiple isosceles trapezoids between myocyte's culture solution feed unit 10, the fluid every
It prevents to be mutually mixed between celliferous extracellular matrix and culture medium from structure 11, but does not influence celliferous extracellular matrix
Mass exchange is carried out between culture medium；Preferably, the upper bottom, bottom of the isosceles trapezoid and 10 ± 2 μm, 20 ± 5 μm a height of
With 10 ± 2 μm.
Refering to Fig. 4-Fig. 5, in a preferred embodiment, the organ chip culture module 3 includes organ chip growing element
18 and organ chip culture solution feed unit 19, the organ chip growing element 18 provided for the growth of cell in organ chip
Growing environment, the organ chip culture solution feed unit 19 provide nutriment supply for the growth of cell in organ chip.
Refering to Fig. 4-Fig. 5, in a preferred embodiment, the organ chip culture mould organ chip growing element 18 in the block
It is provided with the fluid isolation structure lined up by multiple isosceles trapezoids, the fluid between organ chip culture solution feed unit 19
Isolation structure prevents to be mutually mixed between celliferous extracellular matrix and culture medium, but does not influence celliferous extracellular matrix
Mass exchange is carried out between culture medium；Preferably, the upper bottom, bottom of the isosceles trapezoid and 10 ± 2 μm, 20 ± 5 μm a height of
With 10 ± 2 μm.
Refering to Fig. 4-Fig. 5, in a preferred embodiment, the self-circulation system module 2 and the organ chip culture module 3
Between be provided with the fluid isolation structure lined up by multiple isosceles trapezoids, the fluid isolation structure prevents celliferous extracellular
It is mutually mixed between matrix and culture medium, but does not influence to carry out mass exchange between celliferous extracellular matrix and culture medium；
Preferably, the upper bottom, bottom of the isosceles trapezoid and 10 ± 2 μm, 20 ± 5 μm and 10 ± 2 μm a height of.
The lower layer chip 6, the intermediate film 5 and the upper layer chip 1 materials'use but to be not limited only to PDMS (poly-
Dimethyl siloxane)；Preferably, the thickness of the intermediate film 5 is in 250 μm of ± 100 μ ms；Preferably, three-decker is logical
The mode for crossing oxygen plasma treatment bonding assembles, it is preferable that the time of oxygen plasma treatment is in the range of 30s ± 10s.
The extracellular base containing cardiac muscle cell is injected in Myocyte growth unit 9 in cardiac muscle cell's Micropump module 1
Matter, used cardiac muscle cell are selected from but are not limited only to people source cardiac muscle cell, mouse cardiac myocytes and rat myocardial cell, made
Extracellular matrix is selected from but is not limited only to rat-tail I-type collagen, fibrin, pigskin I-type collagen；The cardiac muscle
The basal medium containing growth factor, used basis culture are injected in culture solution supplying module in cell Micropump module 1
Base is selected from but is not limited only to DMEM culture mediums, DMEM/F12 culture solutions, L-15 culture mediums；3 institute of organ chip culture module
The organ structure of simulation is selected from but is not limited only to chip liver, chip lung, chip kidney, chip intestines.
Refering to Fig. 4, in a preferred embodiment, the self-circulation system module 2 includes self-loopa runner 15 and is arranged in institute
State at least one check valve that liquid one-way flowing is maintained on self-loopa runner 15；Preferably, the check valve includes shrinking to expand
Open pipe structure 13, the structure proximate isosceles trapezoid of the convergent divergent channel 13；Preferably, the bottom of the isosceles trapezoid is 0.6
± 0.1mm, upper bottom are 0.2 ± 0.05mm, a height of 2.3 ± 0.2mm.
Refering to Fig. 4, in a preferred embodiment, the self-circulation system module 2 includes being arranged in the self-loopa runner
Pump head chamber 12, the up-down vibration of the intermediate film 5 compresses the volume of the pump head chamber 12, realizes that culture solution is being cultivated
Self-loopa flowing in self-loopa runner 15 described in liquid；Preferably, in oneself of the input side of the pump head chamber 12 and outlet side
Convergent divergent channel structure 13 there are one being respectively set on circulatory flow, the structure proximate isosceles trapezoid of the convergent divergent channel 13.
Below for building a kind of self-loopa liver chip dynamic cultivation device of cardiac muscle cell's Micropump driving, to the present invention
Specific embodiment be described in detail,：
As shown in Figure 1, the present invention is a kind of self-loopa liver chip dynamic cultivation device of cardiac muscle cell's Micropump driving, the dress
It sets including cardiac muscle cell's Micropump module 1, self-circulation system module 2 and liver chip culture module (organ chip culture module 3),
It is the bionics system structure that liver pumps nutriment for realizing heart self-loopa.
As shown in Fig. 2, the processing assembling of the device is realized by following steps：
Structure is made of three-decker, and first, upper layer chip 4 and lower layer chip 6 use common soft lithographic processing method,
This three-decker made designed pattern on silicon chip with SU-8 photoresists with photoetching mechanism before this；Then PDMS silicon rubber is used
Such as existing DOW CORNING Sylgard DC184 products, by its host agent and curing agent with 10:1 ratio is configured to potting syrup, cast
On respective silicon chip masterplate, 85 DEG C of solidification half an hour can be prepared by the chip substrate with microchannel.Finally process
The appearance and size of upper layer chip 4 is 15mm × 10mm × 3mm (length × width × height), the appearance and size of lower layer chip 6 be 20mm ×
20mm × 3mm (length × width × height).Intermediate PDMS film production method is to use PDMS silicon rubber, by its host agent and curing agent with
8:1 ratio is configured to potting syrup, is cast on silicon chip, by sol evenning machine using the rotating speed spin coating 30s of 300-500r/min, 85
DEG C solidification half an hour can be prepared by film of the thickness in 250 μm of ± 100 μ ms.Skill is cleaned finally by based on oxygen plasma
The bonding technology of art assembles three-decker.
As shown in Figure 1,3, the function of cardiac muscle cell's Micropump module 1 is achieved in the following ways：
Cardiac muscle cell's Micropump module 1 is divided into for simulating heart pumping blood function as Myocyte growth
Unit 9 and myocardial cells culture liquid feed unit 10.Wherein Myocyte growth unit 9 provides growth for the growth of cardiac muscle cell
Environment, myocardial cells culture liquid feed unit 10 provide nutriment supply for the growth of cardiac muscle cell.
Extracellular matrix containing cardiac muscle cell is injected by cardiac muscle cell's liquid injection port 7 in Myocyte growth unit 9.Institute
The cardiac muscle cell used includes but are not limited to people source cardiac muscle cell, mouse cardiac myocytes, rat myocardial cell etc..It is used
Extracellular matrix includes but are not limited to rat-tail I-type collagen, fibrin, pigskin I-type collagen etc..It then will be myocardium
The required basal medium containing growth factor of cell growth is injected into cardiac muscle cell by myocardial cells culture liquid liquid injection port 8
In culture solution feed unit 10, used basal medium include but are not limited to DMEM culture mediums, DMEM/F12 culture solutions,
L-15 culture mediums etc..
There are the fluids of multiple isosceles trapezoids between Myocyte growth unit 9 and myocardial cells culture liquid feed unit 10
Isolation structure 11, the upper bottom of isosceles trapezoid, bottom and 10 μm, 20 μm and 10 μm a height of.The effect of fluid isolation structure is to prevent
It is mutually mixed between extracellular matrix and culture medium containing cardiac muscle cell, but does not influence the extracellular matrix containing cardiac muscle cell and training
Mass exchange is carried out between foster base.
As shown in Figure 1,2,3, 4, the function of self-circulation system module is achieved in the following ways：
The self-circulation system module 2 is connected to myocardium Micropump module 1 and liver core for simulating blood of human body flow cycle
Piece culture module (organ chip culture module 3) realizes the dynamic functions of physical supply of liver chip nutriment.
The required basal medium containing growth factor of hepatic cell growth is injected into training by culture solution liquid injection port 14
In nutrient solution self-loopa runner 15, pass through the autonomous of the cardiac muscle cell in 1 cardiac myocyte growing element 9 of cardiac muscle cell's Micropump module
Beating drives the up-down vibration of PDMS film 5, compresses the volume of pump head chamber 12 in self-circulation system module 2, passes through to expand and manage
Collapsible tube structure 13 realizes unidirectional self-loopa flowing of the culture solution in culture solution self-loopa runner 15.
As shown in Figure 1,5, the function of liver chip culture module (organ chip culture module 3) is to be accomplished by the following way
's：
The liver chip culture module (organ chip culture module 3) is for simulating human liver's organ dysfunction, again
It is divided into liver chip growing element (organ chip growing element 18) and (the organ chip culture solution confession of liver chip culture solution feed unit
To unit 19).Wherein liver chip growing element (organ chip growing element 18) provides life for the growth of liver cell in liver chip
Long environment, liver chip culture solution feed unit (organ chip culture solution feed unit 19) are that the growth of liver cell in liver chip carries
It is supplied for nutriment.Then the liver cell being coated in extracellular matrix is injected by liver cell spout reservoir mouth 17
In liver chip growing element (organ chip growing element 18).Used extracellular matrix includes but are not limited to rat-tail I types
Collagen, fibrin, pigskin I-type collagen etc..The required basal medium containing growth factor of hepatic cell growth
Also it is injected into liver chip culture solution feed unit by liver chip culture solution liquid injection port 16.Used basal medium includes
But be not limited only to DMEM culture mediums, DMEM/F12 culture solutions, L-15 culture mediums etc..
Liver chip growing element (organ chip growing element 18) with conscience chip culture solution feed unit (train by organ chip
Nutrient solution feed unit 19) between there are the fluid isolation structure 20 of multiple isosceles trapezoids, the upper bottom of isosceles trapezoid, bottom and a height of
10 μm, 20 μm and 10 μm.The effect of fluid isolation structure is to prevent between extracellular matrix and culture medium containing liver cell mutually
Mixing, but do not influence to carry out mass exchange between extracellular matrix and culture medium containing liver cell.
The above content is specific/preferred embodiment further description made for the present invention is combined, cannot recognize
The specific implementation of the fixed present invention is confined to these explanations.For those of ordinary skill in the art to which the present invention belongs,
Without departing from the inventive concept of the premise, some replacements or modification can also be made to the embodiment that these have been described,
And these are substituted or variant all shall be regarded as belonging to protection scope of the present invention.
Claims (10)
1. a kind of self-loopa organ chip dynamic cultivation device of cardiac muscle cell's Micropump driving, which is characterized in that including from lower
On lamination successively lower layer chip, intermediate film and upper layer chip, the upper layer chip includes cardiac muscle cell's Micropump module, described
Lower layer chip includes self-circulation system module and organ chip culture module, the self-circulation system module and the organ chip
It cultivates module to be interconnected, cardiac muscle cell's Micropump module is for simulating heart pumping blood function, the self-circulation system
Module passes through institute for simulating blood of human body flow cycle, the organ chip culture module for simulating human organ function
Power resources of the autonomous beating of the cardiac muscle cell grown in cardiac muscle cell's Micropump module as the pump housing are stated, the intermediate thin is driven
The up-down vibration of film realizes culture solution in the self-circulation system mould unidirectional self-loopa flowing in the block, to realize to described
The nutrient dynamics of organ chip culture module supply.
2. self-loopa organ chip dynamic cultivation device as described in claim 1, which is characterized in that cardiac muscle cell's Micropump
Module includes Myocyte growth unit and culture solution feed unit, and the Myocyte growth unit is the growth of cardiac muscle cell
Growing environment is provided, the culture solution feed unit provides nutriment supply for the growth of cardiac muscle cell.
3. self-loopa organ chip dynamic cultivation device as claimed in claim 2, which is characterized in that cardiac muscle cell's Micropump
Be provided between mould Myocyte growth unit in the block and culture solution feed unit the fluid lined up by multiple isosceles trapezoids every
From structure, the fluid isolation structure prevents to be mutually mixed between celliferous extracellular matrix and culture medium, but does not influence to contain
Mass exchange is carried out between the extracellular matrix and culture medium of cell；Preferably, the upper bottom, bottom of the isosceles trapezoid and a height of
10 ± 2 μm, 20 ± 5 μm and 10 ± 2 μm.
4. self-loopa organ chip dynamic cultivation device as described in any one of claims 1 to 3, which is characterized in that the device
Official's chip culture module includes organ chip growing element and culture solution feed unit, and the organ chip growing element is organ
The growth of cell provides growing environment in chip, and the culture solution feed unit provides nutrition for the growth of cell in organ chip
Substance supplies.
5. self-loopa organ chip dynamic cultivation device as claimed in claim 4, which is characterized in that the organ chip culture
Be provided between mould organ chip growing element in the block and culture solution feed unit the fluid lined up by multiple isosceles trapezoids every
From structure, the fluid isolation structure prevents to be mutually mixed between celliferous extracellular matrix and culture medium, but does not influence to contain
Mass exchange is carried out between the extracellular matrix and culture medium of cell；Preferably, the upper bottom, bottom of the isosceles trapezoid and a height of
10 ± 2 μm, 20 ± 5 μm and 10 ± 2 μm.
6. such as self-loopa organ chip dynamic cultivation device described in any one of claim 1 to 5, which is characterized in that it is described from
It is provided with the fluid isolation structure lined up by multiple isosceles trapezoids between circulatory system module and the organ chip culture module,
The fluid isolation structure prevents to be mutually mixed between celliferous extracellular matrix and culture medium, but does not influence celliferous thin
Mass exchange is carried out between extracellular matrix and culture medium；Preferably, the upper bottom, bottom of the isosceles trapezoid and it is 10 ± 2 μm a height of,
20 ± 5 μm and 10 ± 2 μm.
7. such as claim 1 to 6 any one of them self-loopa organ chip dynamic cultivation device, which is characterized in that under described
The materials'use PDMS of layer chip, the intermediate film and the upper layer chip；Preferably, the thickness of the intermediate film exists
250 μm of ± 100 μ ms；Preferably, three-decker oxygen plasma treatment bonding by way of assemble, it is preferable that oxygen etc. from
The time of subprocessing is in the range of 30s ± 10s.
8. self-loopa organ chip dynamic cultivation device as claimed in claim 2, which is characterized in that cardiac muscle cell's Micropump
The extracellular matrix containing cardiac muscle cell is injected in mould Myocyte growth unit in the block, used cardiac muscle cell is selected from people source
Cardiac muscle cell, mouse cardiac myocytes and rat myocardial cell, used extracellular matrix are selected from rat-tail I-type collagen, fibre
Fibrillarin, pigskin I-type collagen；Injection contains growth factor in cardiac muscle cell's Micropump mould culture solution supplying module in the block
Basal medium, used basal medium be selected from DMEM culture mediums, DMEM/F12 culture solutions, L-15 culture mediums；It is described
The organ structure that organ chip culture module is simulated is selected from chip liver, chip lung, chip kidney, chip intestines.
9. such as claim 1 to 8 any one of them self-loopa organ chip dynamic cultivation device, which is characterized in that it is described from
Circulatory system module include self-loopa runner and be arranged on the self-loopa runner maintain liquid one-way flowing it is at least one
Check valve；Preferably, the check valve includes convergent divergent channel structure, the structure proximate isosceles trapezoid of the convergent divergent channel；
Preferably, the bottom of the isosceles trapezoid is 0.6 ± 0.1mm, upper bottom is 0.2 ± 0.05mm, a height of 2.3 ± 0.2mm.
10. self-loopa organ chip dynamic cultivation device as described in any one of claim 1 to 9, it is preferable that the self-loopa
System module includes the pump head chamber being arranged in the self-loopa runner, and the up-down vibration of the intermediate film compresses the pump
The volume of head chamber realizes the self-loopa flowing in culture solution self-loopa runner described in culture solution；Preferably, in the pump head
Convergent divergent channel structure there are one being respectively set on the input side of chamber and the self-loopa runner of outlet side, the convergent divergent channel
Structure proximate isosceles trapezoid.
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