CN110511866A - A kind of multiple organ chip and its preparation method and application - Google Patents
A kind of multiple organ chip and its preparation method and application Download PDFInfo
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- CN110511866A CN110511866A CN201810490929.5A CN201810490929A CN110511866A CN 110511866 A CN110511866 A CN 110511866A CN 201810490929 A CN201810490929 A CN 201810490929A CN 110511866 A CN110511866 A CN 110511866A
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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
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Abstract
The invention discloses a kind of multiple organ chips and its preparation method and application, at least two fluid channel groups are equipped in this multiple organ chip, two independent top fluid channels and lower layer's fluid channel are separated by perforated membrane in each fluid channel group, and it is additionally provided with interface channel, for connecting the top fluid channel being located in the group of different fluid channel and lower layer's fluid channel, the top fluid channel and lower layer's fluid channel being located in the group of different fluid channel connect into a fluid channel by interface channel, to have at least three independent fluid channels in this chip, these independent fluid channels can carry out nutrition and mass exchange by perforated membrane again simultaneously, therefore this multiple organ chip can be inoculated at least three kinds of histocytes, and most suitable dynamic cultivation mode can be carried out to the different tissues cell in each fluid channel, To realize the linear interaction of Various Tissues organ.The structure of this multiple organ chip is simple, and production cost is low.
Description
Technical field
The present invention relates to organ bionics techniques fields, and in particular to a kind of multiple organ chip and its preparation method and application.
Background technique
Medicament research and development is a very long and costly process, and most of new drugs fail to can smoothly enter into clinic, main
The reason is that existing all cannot really reflect the intracorporal microenvironment of people based on Cell culture invitro technology and animal model.To understand
Certainly this problem, US National health research center (NIH) in 2012, United States Food and Drag Administration (FDA) and state, the U.S.
Fang Bu advanced research projects agency (DARPA) combines the R&D work for having initiated organ chip (organ-on-chip).
Through research in a few years, it is designed to prepare there are many bionical organ chip, and begins trying for medicine
Object screening, toxicity test etc..On the basis of organ chip, researcher puts forward human body chip (human-on-chip) again, leads to
It crosses and is organically integrated to Different Organs in chip piece, to preferably the effect in vivo such as aids drug and be metabolized
Journey.
Currently, having some study groups and company has developed multiple organ chip, which, will in lower layer
Different cell inoculations combine the fluid of lower layer to form multiple organ and are used in conjunction in the transwell of commercialization.
Existing multiple organ chip does not account for different tissues only by different tissues cell inoculation in different zones
Three-dimensional structure will cause the reduction or missing of some histocyte functions, be two such as the 2-organ-chip of TISSUSE company
Cell culture is tieed up, and the cell cultivated in transwell is in relative quiescent environment.
Other existing multiple organ chips, such as the 10-Organ Chip of Hesperos company, although according to Different Organs
Volume designs the size of corresponding organ culturing room, but chip design and assembling are sufficiently complex, meanwhile, the gravity which selects
Carry out handling liquids and use same culture medium, this method is difficult to meet fluid environment specific to different tissues and nutrition ring
Border.
Summary of the invention
The present invention provides that a kind of structure is simple, can cultivate Various Tissues cell simultaneously, and realizes device associated with multiple organ
Official's chip and its preparation method and application.
According in a first aspect, provide a kind of multiple organ chip in a kind of embodiment, have at least two fluid channel groups and
At least one interface channel, fluid channel group include the top fluid channel being correspondingly arranged and lower layer's fluid channel, top fluid
Perforated membrane is equipped between channel and lower layer's fluid channel, perforated membrane opens top fluid channel and lower layer's fluid channel partition, even
Top fluid channel and the lower layer's fluid channel connection of group is connected in the both ends for connecting road with positioned at different fluid respectively.
According to second aspect, a kind of preparation method of multiple organ chip is provided in a kind of embodiment, which is characterized in that including
Following steps:
Prepare upper layer chip and lower layer chip；
Sealing-in assembling: by porous membrane sealing between upper layer chip and lower layer chip, multiple organ chip is formed.
According to the third aspect, a kind of method for preparing multiple organ combined system is provided in a kind of embodiment, utilization is above-mentioned
Multiple organ chip carry out
Optionally, include the following steps:
The alcohol and ultraviolet rays for being utilized respectively 70% carry out sterilization treatment to above-mentioned multiple organ chip；
Extracellular matrix solution is injected into so modifying in fluid channel perforated membrane and fluid channel, after modification
With the culture medium or PBS flushing channel of serum-free；
According to the different histocyte of the multiple organ to be constructed combination model preparation, and it is inoculated into corresponding fluid respectively
In channel, growth in the fluid channel after making cell adhesion and modification for static 2 hours or more；
Different tissues cell is inoculated into chip simultaneously, or according to the feelings of the growth of different cells, differentiation and maturation
Condition is successively inoculated into corresponding fluid channel sequentially in time；
Corresponding culture medium is selected to the histocyte in different fluid channel, and is filled using corresponding fluid velocity
Stream culture, to simulate the microenvironment of different tissues organ；
Histocyte in different fluid channel is cultivated, by perforated membrane or directly mass exchange is carried out, thus in core
Multiple organ combined system is formed in piece.
According to the multiple organ chip and its preparation method and application of above-described embodiment, at least two are equipped in this multiple organ chip
A fluid channel group, each fluid channel group is interior to be separated into two independent top fluid channels and lower layer's fluid by perforated membrane
Channel, and it is additionally provided with interface channel, for connecting the top fluid channel being located in the group of different fluid channel and lower layer's fluid
Channel, that is, the top fluid channel and lower layer's fluid channel being located in the group of different fluid channel connect into one by interface channel
Fluid channel, to have at least three independent fluid channels in this chip, while these independent fluid channels again can be with
Nutrition and mass exchange are carried out by perforated membrane, therefore this multiple organ chip can be inoculated at least three kinds of histocytes, and can be with
Most suitable dynamic cultivation mode is carried out to the different tissues cell in each fluid channel, to realize the linear of Various Tissues organ
Interaction.The structure of this multiple organ chip is simple, and production cost is low.
Detailed description of the invention
Fig. 1 is the structural schematic diagram that the upper layer chip of multiple organ chip and lower layer chip are half-and-half opened in embodiment one；
Fig. 2 is the cross section structure schematic diagram of multiple organ chip in embodiment one；
Fig. 3 is the structural schematic diagram that the upper layer chip of multiple organ chip and lower layer chip are half-and-half opened in other embodiments；
Fig. 4 is the cross section structure schematic diagram of multiple organ chip in other embodiments；
Fig. 5 is the flow chart of multiple organ chip preparation method in embodiment two；
Fig. 6 is the flow chart of embodiment two chip and lower layer chip preparation method at the middle and upper levels；
Fig. 7 is the flow chart of porous membrane sealing in embodiment two.
Specific embodiment
Below by specific embodiment combination attached drawing, invention is further described in detail.
Embodiment one:
A kind of multiple organ chip is present embodiments provided, this multiple organ chip is three-decker, and there are three independent streams for tool
Body channel dynamic can cultivate three kinds of organ cells simultaneously, be suitable for the fields of biomedicine researchs such as drug screening, food safety.
As shown in Figure 1, the multiple organ chip of the present embodiment includes upper layer chip 110 and lower layer chip 120, upper layer chip
There are two open top fluid channels 111 and 112 for 110 lower surface tool, and there are two open for the upper surface tool of lower layer chip 120
Lower layer's fluid channel 121 and 122, top fluid channel 111 and 112 is correspondingly arranged with lower layer fluid channel 121 and 122, shape
At two fluid channel groups, the one fluid channel group of composition corresponding with lower layer's fluid channel 121 of top fluid channel 111, upper layer
Another fluid channel group of composition corresponding with lower layer's fluid channel 122 of fluid channel 112.Upper layer chip 110 is additionally provided with open
Interface channel 130, in the present embodiment, interface channel 130 is extended by top fluid channel 112, one end of interface channel 130
It connect conducting with the end in top fluid channel 112, the other end, which is extended to, connect conducting with the end of lower layer fluid channel 121.
As shown in Fig. 2, being sealed between the upper layer chip 110 and lower layer chip 120 of the multiple organ chip of the present embodiment more
Open fluid channel encloses closing in pore membrane 140, upper layer chip 110 and lower layer chip 120, and perforated membrane 140 is by upper stream
Body channel and lower layer's fluid channel partition are opened, and carry out the mass exchange between fluid channel by perforated membrane 140.Interface channel
Top fluid channel 112 and lower layer's fluid channel 121 are connected into a fluid channel by 130, so that this multiple organ chip has
Three independent fluid channels, respectively top fluid channel 111, top fluid channel 112 are connect with lower layer fluid channel 121
At fluid channel, lower layer's fluid channel 122, three fluid channels can realize mass exchange by perforated membrane 140, can be near
Few three kinds of histocytes are seeded in the independent fluid pathways of this multiple organ chip, can simulate the phase interaction between three kinds of tissues
With.In interface channel 130 with settable perforated membrane 140 at the docking of lower layer fluid channel 121, or in interface channel 130
It is not provided with perforated membrane 140.
In the present embodiment, beaten on upper layer chip 110 there are six hole, respectively with the both ends pair of three independent fluid pathways
It answers, so that three independent fluid pathways are respectively provided with respective stream socket.
In other embodiments, as shown in Figure 3 and Figure 4, there are three upper respectively in upper layer chip 110 and lower layer chip 120
Layer fluid channel and three lower layer's fluid channels form three fluid channel groups, and logical in two groups of adjacent Liang Ge lower layer fluids
It is equipped with interface channel between lower layer's fluid channel and top fluid channel in road, is sealed among upper layer chip 110 and lower layer chip 120
Connect it is porous, in this multiple organ chip formed 4 independent fluid channels, and adjacent flow channels arrive between can be by porous
Film 140 carries out mass exchange.This multiple organ chip can be inoculated at least four kinds of histocytes, mould in 4 independent fluid channels
The interaction of organ in quasi- 4.
In other embodiments, the fluid that other different numbers are arranged in top fluid channel and lower layer's fluid channel is logical
Road, and channel size can be designed according to the volume of required Different Organs, to meet the simulation of greater number organ cell, improve
The flux of chip.Interface channel 130 can also be arranged in lower layer chip 120, lower layer's fluid channel of lower layer chip is extended
Setting is formed.
In the present embodiment, the length of top fluid channel and lower layer's fluid channel is about 5-15 millimeters, wide about 0.5-1 milli
Rice, 0.1-0.5 millimeters of Gao Yuewei.Upper layer chip 110 and lower layer chip 120 are the materials such as PDMS, SEBS, PMMA, PS or PE.
The aperture of through-hole is about 0.22-10 microns on perforated membrane 140, and the diameter of through-hole is 0.5-1.5 millimeters, perforated membrane
140 be polymer material film or biological material film.Polymer material film includes at least PC, cellulose nitrate and PET, biological material film
Including at least alginic acid, chitosan, collagen and gelatin.
In the present embodiment, multiple organ chip passes through the setting of two fluid channel groups and interface channel, forms three solely
Vertical fluid channel, three fluid channels can realize mass exchange by perforated membrane 140, three kinds of histocytes can at least will connect
Kind can simulate the interaction between three kinds of tissues in the independent fluid pathways of this multiple organ chip.And this multiple organ core
The structure of piece is simple, and production cost is low.
Embodiment two:
A kind of preparation method of multiple organ chip is present embodiments provided, this preparation method mainly uses soft lithography system
Multiple organ chip in standby above-described embodiment one.
As shown in figure 5, the preparation method of the multiple organ chip of the present embodiment mainly includes the following steps:
S100: preparation upper layer chip and lower layer chip；
S200: sealing-in assembling.
In step S200, by porous membrane sealing between the upper layer chip and lower layer chip, multiple organ chip is formed.
Specifically, as shown in fig. 6, step S100 (preparation upper layer chip and lower layer chip) includes the following steps:
S101: in glass or the substrate surface spin coating photoresist of silicon wafer, and front baking is carried out；
Preferred SU-8 photoresist in the present embodiment, SU-8 photoresist are a kind of epoxy type, the negative photoresist of black light,
SU-8 photoresist absorptivity in near-ultraviolet range is low, so that all having preferable exposure uniform on photoresist thickness
Property, the structure of graphic edge near vertical can be obtained.
The mechanism of SU-8 photoresist photoetching is as follows: the photoinitiator in photoresist absorbs photon and is chemically reacted, raw
A kind of strong acid is produced, effect is that front baking is used as acid catalyst to promote cross-linking reaction in the process.Only in the photoresist of exposure area
It is middle just to generate strong acid, therefore reaction is just crosslinked only in exposure area, the crosslinking reaction may not occur in unexposed region, and
Photoresist does not dissolve in developer solution after crosslinking reaction, and photoresist does not crosslink the developer solution that is dissolved in of reaction, therefore develops
Photoresist afterwards forms the figure opposite with mask pattern.
In this step, spin coating SU-8 photoresist with a thickness of 200 microns, with top fluid channel and lower layer's fluid channel
Height is corresponding.The temperature of front baking is 95 DEG C, and the time is 2 hours.
S102: the exposure mask with upper and lower level chip structure pattern is fixed on to the substrate surface with photoresist；
Exposure mask has upper and lower level chip structure pattern, have on upper and lower level chip structure pattern top fluid channel design and
Lower layer's fluid channel structure, pattern is corresponding with the fluid channel of upper layer chip and lower layer chip, and exposure mask is used for baffle ultraviolet light, from
And pattern on exposure mask is copied on SU-8 photoresist.
S103: light source vertical irradiation is exposed with the glass or silicon wafer of exposure mask and photoresist, and is dried after carrying out；
The pattern that ultraviolet light passes through on exposure mask is irradiated on SU-8 photoresist, and the region that SU-8 photoresist is exposed will occur
Crosslinking, the region after crosslinking do not dissolve in developer solution.In the present embodiment, light source is ultraviolet source, is carried out for emitting ultraviolet light
Exposure.
In this step, the temperature dried afterwards is 95 DEG C, and the time is 10 minutes.
S104: after natural cooling, unexposed photoresist is removed using ethyl lactate developer solution, it is logical to form layer fluid up and down
The template of road structure, and carry out post bake；
In this step, unexposed SU-8 photoresist is removed by developer solution, the SU-8 photoresist after development is formed and covered
The opposite graphic structure of film, then post bake are reinforced, and the temperature of post bake is 180 DEG C, and the time is 2 hours.
S105: upper layer chip and lower layer chip are prepared by the template with upper and lower level chip structure.
In this step, pass through top fluid channel design, lower layer's fluid channel structure and connecting pipeline structure inverse structure
Photoetching glue pattern plate prepare the upper layer chip and lower layer chip of PDMS material, upper layer chip and lower layer chip respectively include two solely
Vertical fluid channel, and punched in upper layer chip designated position, the access hole of formation upper and lower level fluid channel, and lower layer chip
It does not punch.It is finally completed and is prepared into upper layer chip and lower layer chip.
As shown in fig. 7, step S200 (sealing-in assembling) includes the following steps:
S201: by porous membrane sealing on the chip of upper layer；
Perforated membrane is fixed on the chip of upper layer by way of hot pressing or bonding,
S202: by lower layer chip alignment sealing-in in the other side of perforated membrane, multiple organ chip is formed.
Lower layer chip is aligned with the upper layer chip with perforated membrane, is fixed by way of hot pressing or bonding, lower layer's core
Piece sealing-in is in the other side of perforated membrane.Perforated membrane is PC film, can also be the film of the materials such as PDMS.
Intersection in adjacent lower fluid channel Yu top fluid channel is equipped with through-hole, and the perforated membrane of through hole can be protected
It stays, the perforated membrane of through hole can also be removed.
The preparation method of multiple organ chip provided in this embodiment mainly prepares multiple organ chip using soft lithography,
Preparation efficiency is high, and SU-8 photoresist is selected to be prepared, and can prepare the high chip of structure precision.
Embodiment three:
A kind of method for preparing multiple organ combined system is present embodiments provided, this method is to answer multiple organ chip
With.
The method that the present embodiment prepares multiple organ combined system utilizes the independent fluid pathways containing there are three in embodiment one
Multiple organ chip carry out, building multiple organ be combined system, specifically comprise the following steps:
S301: the alcohol and ultraviolet rays for being utilized respectively 70% carry out at sterilizing chip described in embodiment one
Reason；
S302: extracellular matrix solution (type i collagen, matrigel matrigel etc.) is logical from two fluids on chip upper layer
Road entrance, which is injected into channel, modifies perforated membrane；By extracellular matrix solution (type i collagen, matrigel matrigel etc.)
From chip upper layer, fluid inlet injection chip lower layer fluid channel identical with lower layer's fluid channel carries out lower layer's fluid channel
The culture medium or PBS flushing channel of serum-free are used in modification after modification；
S303: by enterocyte (Caco-2) according to 106The concentration of a/ml is inoculated into 111 in chip top fluid channel, quiet
Grow cell adhesion on the perforated membrane 140 after modification；
S304: perfusion culture is carried out to enterocyte (Caco-2), enterocyte (Caco-2) is by differentiation and maturation, In after 5-7 days
Chip upper layer forms enteron aisle micro-assembly robot；
S305: again by vascular endothelial cell (HUVEC) according to 106The concentration of a/ml is inoculated into chip top fluid channel
Interior 112, grow cell adhesion on the perforated membrane 140 after modification；
S306: again by liver cell (HepG2) according to 106The concentration of a/ml is inoculated into 122 in chip lower layer fluid channel,
Make within static 2 hours or more lower channel bottom surface of the cell adhesion after modification；
S307: carrying out perfusion culture simultaneously to three kinds of cells, form three organ combined system of intestines-blood vessel-liver in the chip,
And it can be applied to the correlative studys such as drug absorption, metabolism and pharmacokinetics work.
" intestines-blood vessel-liver " three organs connection system is with being to simulate intracorporal Absorption And Metabolism function.Firstly, enterocyte is in chip
The intestinal tissue of interior formation has absorption function, the substance in intestines organ fluid channel can be transported blood vessel access by perforated membrane
Interior, this process is simulation absorption function；Substance into blood vessel penetrates blood vessel again, enters in liver channel, simulates blood circulation
Process；Finally, the substance absorbed has arrived in liver channel, metabolite is formed after the liver cell metabolism being cultured.This chip structure
It has built and has simulated the flux of absorption of human body metabolism, multiple organs are cascaded by chip, and formation is a single-phase access.It is real
When testing, related tissue can be seeded in respectively in connected channel according to the metabolic pathway to be constructed.
After the three organ combined system of intestines-blood vessel-liver of the present embodiment is for investigating oral drugs by intestinal absorption, hepatic metabolism
Whether there is side effect to kidney.
In other embodiments, multiple organ combined system can be used for the combination of other organs of human body, human body possess 10 kinds with
On organ type, including liver, intestines, the heart, kidney, brain, lung and reproductive system, immune system, vascular system and skin etc..Root
According to the sequencing run between intracorporeal organ, the assembling of a variety of organ models is organically integrated into chip piece.Such as: mould
The metabolic process of quasi- oral drugs, can construct intestines-liver-target organ-side effect organ combination, wherein target organ in the chip
It may include: heart, brain, lung, kidney, blood-brain barrier, placental barrier etc., side effect organ may include: liver, kidney, heart etc..
Use above specific case is illustrated the present invention, is merely used to help understand the present invention, not to limit
The system present invention.For those skilled in the art, according to the thought of the present invention, can also make several simple
It deduces, deform or replaces.
Claims (10)
1. a kind of multiple organ chip, which is characterized in that there is at least two fluid channel groups and at least one interface channel, it is described
Fluid channel group includes the top fluid channel being correspondingly arranged and lower layer's fluid channel, the top fluid channel and lower layer's fluid
Perforated membrane is equipped between channel, the perforated membrane opens the top fluid channel and lower layer's fluid channel partition, the connection
Top fluid channel and the lower layer's fluid channel connection of group is connected in the both ends in channel with positioned at different fluid respectively.
2. multiple organ chip as described in claim 1, which is characterized in that including upper layer chip and lower layer chip, the upper layer
The lower surface of chip has at least two open top fluid channels and at least one interface channel opened；Lower layer's core
The upper surface of piece has at least two open lower layer's fluid channels；Upper layer chip fluid channel and lower layer's fluid channel phase
It is corresponding, at least two fluid channel groups are formed, one end of the interface channel of the opening is connect with open top fluid channel,
The other end is corresponding with lower layer's fluid channel of opening of other fluid channel groups is located at；Between the upper layer chip and lower layer chip
It is sealed with perforated membrane, the perforated membrane opens top fluid channel and lower layer's fluid channel partition.
3. multiple organ chip as claimed in claim 2, which is characterized in that the top fluid channel and lower layer's fluid channel
Length is 5-15 millimeters, and width is 0.5-1 millimeters, 0.1-0.5 millimeters a height of；The aperture of the perforated membrane is 0.22-10 microns, is led to
The diameter in hole is 0.5-1.5 millimeters.
4. multiple organ chip as claimed in claim 2, which is characterized in that the upper layer chip and lower layer chip be PDMS,
SEBS, PMMA, PS or PE material；The perforated membrane is polymer material film or biological material film, and the polymer material film is extremely
It less include PC, cellulose nitrate and PET, the biological material film includes at least alginic acid, chitosan, collagen and gelatin.
5. a kind of preparation method of multiple organ chip, is used to prepare multiple organ core according to any one of claims 1 to 4
Piece, which comprises the steps of:
Prepare upper layer chip and lower layer chip；
Sealing-in assembling: by porous membrane sealing between the upper layer chip and lower layer chip, multiple organ chip is formed.
6. preparation method as claimed in claim 5, which is characterized in that the preparation upper layer chip and lower layer chip are including as follows
Step:
In glass or the substrate surface spin coating photoresist of silicon wafer, and carry out front baking；
Exposure mask with upper and lower level chip structure pattern is fixed on to the substrate surface with photoresist；
Light source vertical irradiation is exposed with the glass or silicon wafer of exposure mask and photoresist, and is dried after carrying out；
After natural cooling, unexposed photoresist is removed using developer solution, forms the template with upper and lower level fluid channel structure,
And carry out post bake；
Upper layer chip and lower layer chip are prepared by the template with upper and lower level chip structure.
7. preparation method as claimed in claim 6, which is characterized in that the photoresist is SU-8 photoresist, the developer solution
For ethyl lactate, the photoresist with a thickness of 100-500 microns；The light source is ultraviolet source.
8. preparation method as claimed in claim 6, which is characterized in that the temperature of the front baking is 95 DEG C, and the time is that 2-8 is small
When, the temperature dried after described is 95 DEG C, and the time is 10-30 minutes, and the temperature of the post bake is 180 DEG C, and the time is 2 hours.
9. preparation method as claimed in claim 5, which is characterized in that the sealing-in assembling includes the following steps:
By perforated membrane by way of hot pressing or bonding sealing-in on the chip of upper layer；
By lower layer chip alignment sealing-in in the other side of perforated membrane, multiple organ chip is formed.
10. a kind of method for preparing multiple organ combined system, which is characterized in that using described in any one of any one of claims 1 to 44
Multiple organ chip carries out；
Optionally, include the following steps:
The alcohol and ultraviolet rays for being utilized respectively 70% carry out the described in any item multiple organ chips of such as Claims 1-4
Sterilization treatment；
Extracellular matrix solution is injected into the fluid channel, perforated membrane and fluid channel are modified, nothing is used after modification
The culture medium or PBS flushing channel of serum；
According to the different histocyte of the multiple organ to be constructed combination model preparation, and it is inoculated into corresponding fluid channel respectively
It is interior, growth in the fluid channel after making cell adhesion and modification for static 2 hours or more；
Different tissues cell is inoculated into chip simultaneously, or according to the situation of the growth of different cells, differentiation and maturation, is pressed
It is successively inoculated into corresponding fluid channel according to time sequencing；
Corresponding culture medium is selected to the histocyte in different fluid channel, and carries out perfusion training using corresponding fluid velocity
It supports, to simulate the microenvironment of different tissues organ；
Histocyte in different fluid channel is cultivated, by perforated membrane or directly mass exchange is carried out, thus in the chip
Form multiple organ combined system.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111363682A (en) * | 2020-04-22 | 2020-07-03 | 苏州济研生物医药科技有限公司 | Organ chip with multilayer combined structure and use method thereof |
| CN113926498A (en) * | 2021-11-04 | 2022-01-14 | 田甜 | Preparation method of laminar flow low-shear force micro-fluidic chip capable of promoting brain-like organ maturation |
| CN115747060A (en) * | 2022-11-30 | 2023-03-07 | 苏州大学 | Universal organ chip module and three-dimensional multi-organ chip |
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