CN220166205U - Organ-like co-culture chip - Google Patents
Organ-like co-culture chip Download PDFInfo
- Publication number
- CN220166205U CN220166205U CN202320652114.9U CN202320652114U CN220166205U CN 220166205 U CN220166205 U CN 220166205U CN 202320652114 U CN202320652114 U CN 202320652114U CN 220166205 U CN220166205 U CN 220166205U
- Authority
- CN
- China
- Prior art keywords
- cell culture
- culture
- culture area
- area
- chip
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000003501 co-culture Methods 0.000 title claims abstract description 60
- 238000004113 cell culture Methods 0.000 claims abstract description 112
- 210000002220 organoid Anatomy 0.000 claims abstract description 45
- 210000003556 vascular endothelial cell Anatomy 0.000 claims abstract description 33
- 210000002865 immune cell Anatomy 0.000 claims abstract description 25
- 210000000601 blood cell Anatomy 0.000 claims abstract description 22
- 239000007788 liquid Substances 0.000 claims abstract description 20
- 108010082117 matrigel Proteins 0.000 claims abstract description 13
- 239000000758 substrate Substances 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 9
- 239000012528 membrane Substances 0.000 claims description 9
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 8
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 8
- 239000012530 fluid Substances 0.000 claims description 8
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims description 8
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 claims description 8
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 8
- 239000011521 glass Substances 0.000 claims description 4
- 238000004891 communication Methods 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 15
- 210000000056 organ Anatomy 0.000 abstract description 12
- 210000001519 tissue Anatomy 0.000 abstract description 11
- 210000004204 blood vessel Anatomy 0.000 abstract description 4
- 239000011159 matrix material Substances 0.000 abstract description 4
- 230000004083 survival effect Effects 0.000 abstract description 2
- 238000000034 method Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 230000005305 organ development Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000025366 tissue development Effects 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 230000004791 biological behavior Effects 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000010362 genome editing Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
Abstract
The utility model relates to the technical field of biological tissue engineering, in particular to an organoid co-culture chip. The organ co-culture chip comprises a matrix and a chip main body above the matrix; the chip main body comprises a first cell culture area, a second cell culture area, a vascular endothelial cell culture area, an immune cell and blood cell culture area, a liquid flow inlet and a liquid flow outlet; the vascular endothelial cell culture area is arranged outside the first cell culture area and the second cell culture area, and the immune cells and the blood cell culture area are arranged outside the vascular endothelial cell culture area; the liquid flow inlet and the liquid flow outlet are communicated with the immune cells and the blood cell culture area; the first cell culture area and the second cell culture area are communicated through a co-culture channel constructed by matrigel. The organoid co-culture chip can better promote tissue culture and survival, blood vessels and immune cell microenvironments exist around each organoid, and microenvironments required by growth can be provided for cells.
Description
Technical Field
The utility model relates to the technical field of biological tissue engineering, in particular to an organoid co-culture chip.
Background
Organoids (organoids) are three-dimensional cell complexes formed by induced differentiation of stem cells or organ progenitor cells in vitro using 3D culture techniques that resemble the organ or tissue of interest in both structure and function, and which possess stable phenotypic and genetic characteristics that enable long-term culture in vitro. The organoids can simulate the genetic characteristics and apparent characteristics of target tissues or organs to a great extent, and have wide application prospects in the fields of organ development, accurate medical treatment, regenerative medicine, drug screening, gene editing, disease modeling and the like. However, conventional methods of culturing stem cells to form organoids that rely on 3D culture techniques with sequential addition of growth factors still have limitations such as their imprecise control over organoids and their local environment, and furthermore, the method does not replicate well the complex and dynamic microenvironment of the organ development process, which is precisely the contributory factor to organogenesis, which makes it difficult to obtain a more complete organoid process resembling organ development in vivo.
The organoid chip is a special chip technology based on cell 3D culture and matched with a microfluidic system, and combines cell-cell interaction, matrix characteristics and biochemical and biomechanical characteristics to simulate and construct a three-dimensional organ physiological microsystem on the chip. The organoid chip truly reproduces the physiological and pathological activities of human organs in a brand-new way, so that people can intuitively observe and research various biological behaviors of organisms, provide a new view angle for understanding biological mechanisms of new drug targets and researching diseases, and simultaneously provide a new method for predicting the effectiveness and safety of new drugs and exploring the differences and unexpected clinical manifestations of species. At present, a conventional organoid chip constructs an immune microenvironment by co-culturing a tumor organoid and immune cells, but cannot truly simulate a real organ in-vivo microenvironment and organ-to-organ interaction.
Disclosure of Invention
The utility model aims to provide an organoid co-culture chip. The organoid co-culture chip has the advantages of small volume, less reagent consumption, easy realization of automation and high-throughput treatment, capability of supporting the co-culture of multiple organs and the like. In addition, the organ-like co-culture chip not only can simulate the interaction between tissues, but also can simulate blood vessels and immune microenvironments existing around tissues in a body, blood vessels and immune cell microenvironments exist around each organ-like, and the organ-like obtained by culture is more suitable for related researches such as tissue development, drug safety evaluation, drug permeation and the like.
In order to achieve the above purpose, the present utility model adopts the following technical scheme:
an organoid co-culture chip comprises a substrate and a chip main body above the substrate; the chip main body comprises a first cell culture area, a second cell culture area, a vascular endothelial cell culture area, an immune cell and blood cell culture area, a liquid flow inlet and a liquid flow outlet; the first cell culture area and the second cell culture area are communicated through a co-culture channel constructed by matrigel; the vascular endothelial cell culture area is arranged outside the first cell culture area and the second cell culture area; the immune cells and the blood cells are in the outer side of the vascular endothelial cell culture area and the co-culture channel; the fluid inlet and the fluid outlet are in communication with the immune cell and blood cell culture area.
Further, the substrate is a glass slide.
Further, the chip main body is made of PDMS material.
Further, the first cell culture section and the second cell culture section are circular-hole-shaped.
Preferably, the diameter of the round hole is 5-30mm.
Further, the co-culture channel is of a linear structure.
Further, the length of the straight line structure is 3-10mm.
Further, the co-culture channel is an annular structure, and the co-culture channel surrounds the first cell culture area or the second cell culture area for one or more circles. The co-culture channel is arranged to be of an annular structure, so that organ/tissue connection between long distances can be better simulated, and the maximum layering degree reduces the volume of the chip on the basis of increasing the acting distance between organs.
Further, the first cell culture area and the vascular endothelial cell culture area, and the second cell culture area and the vascular endothelial cell culture area are respectively isolated by a permeable membrane.
Furthermore, the vascular endothelial cell culture area is constructed by matrigel.
The beneficial effects of the utility model are as follows:
1. the organoid co-culture chip has the advantages of small volume, less reagent consumption, easy realization of automation and high-flux culture; the organoid co-culture chip supports the co-culture of various organs/tissues, and the chip can be adjusted according to the variety of the cultured organoids so as to better simulate the interaction between organs/tissues with short distance or long distance.
2. The organoid co-culture chip can better promote tissue culture and survival, blood vessels and immune cell microenvironments exist around each organoid, and microenvironments required by growth can be provided for cells; the organoids obtained by co-culture with the chip of the utility model are more suitable for relevant researches such as tissue development, drug safety evaluation, drug permeation and the like.
Drawings
FIG. 1 is a schematic diagram of the structure of an organoid co-culture chip according to example 1 of the present utility model;
FIG. 2 is a top view of the chip body of the organoid co-culture chip of example 1 of the utility model;
FIG. 3 is a schematic diagram of the structure of an organoid co-culture chip according to example 2 of the present utility model;
FIG. 4 is a top view of the chip body of the organoid co-culture chip of example 2 of the utility model;
in the figure: 1-matrix, 2-chip body, 2.1-first cell culture zone, 2.2-second cell culture zone, 2.3-vascular endothelial cell culture zone, 2.4-immune cell and blood cell culture zone, 2.5-liquid inlet, 2.6-liquid outlet, 2.7-co-culture channel and 2.8-permeable membrane.
Detailed Description
In order to more clearly illustrate the embodiments of the present utility model or the technical solutions in the prior art, the present utility model will be further described below with reference to specific embodiments and drawings, and it is obvious that the drawings in the following description are only some embodiments of the present utility model, and other drawings can be obtained according to these drawings without inventive effort for a person skilled in the art.
It is to be understood that the terms "upper," "lower," "front," "rear," "left," "right," "horizontal," "top," "inner," "outer," and the like indicate or are based on the orientation or positional relationship shown in the drawings, merely to facilitate describing the present utility model and simplify the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus should not be construed as limiting the present utility model.
The terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first", "a second", or a third "may explicitly or implicitly include one or more such feature. In the description of the present utility model, unless otherwise indicated, the meaning of "a group" is two or more.
Example 1
An organ-like co-culture chip, the structure of which is shown in figure 1, comprises a basal body 1 and a chip main body 2 above the basal body; a top view of the chip body is shown in fig. 2. The chip main body 2 comprises a first cell culture area 2.1, a second cell culture area 2.2, a vascular endothelial cell culture area 2.3, an immune cell and blood cell culture area 2.4, a liquid flow inlet 2.5 and a liquid flow outlet 2.6; the first cell culture area 2.1 and the second cell culture area 2.2 are communicated through a co-culture channel 2.7 constructed by matrigel; the vascular endothelial cell culture area 2.3 is arranged outside the first cell culture area 2.1 and the second cell culture area 2.2, and the immune cells and the blood cell culture area 2.4 are arranged outside the vascular endothelial cell culture area 2.3 and the co-culture channel 2.7; the liquid flow inlet 2.5 and the liquid flow outlet 2.6 are communicated with the immune cells and blood cell culture area 2.4; the first cell culture area 2.1 and the vascular endothelial cell culture area 2.3, and the second cell culture area 2.2 and the vascular endothelial cell culture area 2.3 are respectively isolated by a permeable membrane 2.8;
the substrate 1 is a glass slide; the co-culture channel 2.7 is of a linear structure; the length of the linear structure is 5mm; the first cell culture area and the second cell culture area are round holes, and the diameter of each round hole is 10mm; the vascular endothelial cell culture area is constructed by matrigel; the chip main body is made of PDMS material.
The construction method of the organoid co-culture chip comprises the following steps:
step A1: selecting a substrate 1, superposing a layer of PDMS material on the substrate 1 to construct a chip main body 2, and perforating the inside of the PDMS material to form a liquid flow inlet 2.5, a liquid flow outlet 2.6 and a culture area 2.4 of immune cells and blood cells;
step A2: constructing a first cell culture area 2.1 and a second cell culture area 2.2 by using a permeable membrane 2.8 in a culture area 2.4 of immune cells and blood cells, constructing a co-culture channel 2.7 by using matrigel, and communicating the first cell culture area 2.1 with the second cell culture area 2.2 by using the co-culture channel 2.7;
step A3: the vascular endothelial cell culture zone 2.3 was constructed with matrigel outside the permeable membrane 2.8.
The application method of the organoid co-culture chip comprises the following steps:
step B1: adding vascular endothelial cells into a vascular endothelial cell culture area, and respectively adding first cells and second cells carrying culture media from the centers of the first cell culture area and the second cell culture area after the cells adhere to the wall; the first cell is a liver organoid and the second cell is a bile duct organoid.
Step B2: the mixture of immune cells and blood cells carrying the culture medium is added from the fluid inlet for culture.
Example 2
An organ-like co-culture chip, the structure of which is shown in figure 3, comprises a basal body 1 and a chip main body 2 above the basal body; as shown in fig. 4, the chip body 2 includes a first cell culture area 2.1, a second cell culture area 2.2, a vascular endothelial cell culture area 2.3, an immune cell and blood cell culture area 2.4, a fluid inlet 2.5 and a fluid outlet 2.6; the first cell culture area 2.1 and the second cell culture area 2.2 are communicated through a co-culture channel 2.7 constructed by matrigel; the vascular endothelial cell culture area 2.3 is arranged outside the first cell culture area 2.1 and the second cell culture area 2.2, and the immune cells and the blood cell culture area 2.4 are arranged outside the vascular endothelial cell culture area 2.3 and the co-culture channel 2.7; the liquid flow inlet 2.5 and the liquid flow outlet 2.6 are communicated with the immune cells and blood cell culture area 2.4; the first cell culture area 2.1 and the vascular endothelial cell culture area 2.3, and the second cell culture area 2.2 and the vascular endothelial cell culture area 2.3 are respectively isolated by a permeable membrane 2.8;
the substrate 1 is a glass slide; the co-culture channel 2.7 is of an annular structure, and the co-culture channel 2.7 surrounds the second cell culture area 2.2 for one circle; the first cell culture area and the second cell culture area are round holes, and the diameter of each round hole is 10mm; the vascular endothelial cell culture area is constructed by matrigel. The chip main body is made of PDMS material.
The construction method of the organoid co-culture chip comprises the following steps:
step A1: selecting a substrate 1, superposing a layer of PDMS material on the substrate 1 to construct a chip main body 2, and perforating the inside of the PDMS material to form a liquid flow inlet 2.5, a liquid flow outlet 2.6 and a culture area 2.4 of immune cells and blood cells;
step A2: constructing a first cell culture area 2.1 and a second cell culture area 2.2 by using a permeable membrane 2.8 in a culture area 2.4 of immune cells and blood cells, constructing a co-culture channel 2.7 by using matrigel, and communicating the first cell culture area 2.1 with the second cell culture area 2.2 by using the co-culture channel 2.7;
step A3: the vascular endothelial cell culture zone 2.3 was constructed with matrigel outside the permeable membrane 2.8.
The application method of the organoid co-culture chip comprises the following steps:
step B1: adding vascular endothelial cells into a vascular endothelial cell culture area, and respectively adding first cells and second cells carrying culture media from the centers of the first cell culture area and the second cell culture area after the cells adhere to the wall; the first cell is a cerebral cortex organoid and the second cell is a spinal organoid.
Step B2: the mixture of immune cells and blood cells carrying the culture medium is added from the fluid inlet for culture.
The foregoing examples merely represent preferred embodiments of the present utility model, which are described in more detail and are not to be construed as limiting the scope of the utility model. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the utility model, which are all within the scope of the utility model. Accordingly, the scope of protection of the present utility model is to be determined by the appended claims.
Claims (10)
1. An organoid co-culture chip, which is characterized by comprising a substrate (1) and a chip main body (2) above the substrate; the chip main body (2) comprises a first cell culture area (2.1), a second cell culture area (2.2), a vascular endothelial cell culture area (2.3), an immune cell and blood cell culture area (2.4), a liquid flow inlet (2.5) and a liquid flow outlet (2.6); the first cell culture area (2.1) and the second cell culture area (2.2) are communicated through a co-culture channel (2.7) constructed by matrigel; the vascular endothelial cell culture area (2.3) is arranged outside the first cell culture area (2.1) and the second cell culture area (2.2), and the immune cell and blood cell culture area (2.4) is arranged outside the vascular endothelial cell culture area (2.3) and the co-culture channel (2.7); the fluid inlet (2.5) and the fluid outlet (2.6) are in communication with the immune cell and blood cell culture zone (2.4).
2. The organoid co-culture chip according to claim 1, characterized in that the substrate (1) is a glass slide.
3. The organoid co-culture chip according to claim 1, characterized in that the material of the chip body (2) is PDMS material.
4. The organoid co-culture chip according to claim 1, wherein the first cell culture zone (2.1) and the second cell culture zone (2.2) are circular-hole-shaped.
5. The organoid co-culture chip of claim 4, wherein the circular aperture has a diameter of 5-30mm.
6. Organoid co-culture chip according to claim 1, characterized in that the co-culture channel (2.7) is of rectilinear structure.
7. The organoid co-culture chip of claim 6, wherein the linear structure has a length of 3-10mm.
8. The organoid co-culture chip according to claim 1, characterized in that the co-culture channel (2.7) is of annular configuration, the co-culture channel (2.7) surrounding the first cell culture zone (2.1) or the second cell culture zone (2.2) one or more turns.
9. The organoid co-culture chip according to claim 1, wherein the first cell culture zone (2.1) and the vascular endothelial cell culture zone (2.3) and the second cell culture zone (2.2) and the vascular endothelial cell culture zone (2.3) are separated by a permeable membrane (2.8), respectively.
10. The organoid co-culture chip according to claim 1, wherein said vascular endothelial cell culture zone (2.3) is constituted by matrigel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202320652114.9U CN220166205U (en) | 2023-03-28 | 2023-03-28 | Organ-like co-culture chip |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202320652114.9U CN220166205U (en) | 2023-03-28 | 2023-03-28 | Organ-like co-culture chip |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN220166205U true CN220166205U (en) | 2023-12-12 |
Family
ID=89058760
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202320652114.9U Active CN220166205U (en) | 2023-03-28 | 2023-03-28 | Organ-like co-culture chip |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN220166205U (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117417831A (en) * | 2023-12-18 | 2024-01-19 | 芯潮澎湃生物科技(南京)有限公司 | Co-immune culture organoid chip model |
-
2023
- 2023-03-28 CN CN202320652114.9U patent/CN220166205U/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117417831A (en) * | 2023-12-18 | 2024-01-19 | 芯潮澎湃生物科技(南京)有限公司 | Co-immune culture organoid chip model |
| CN117417831B (en) * | 2023-12-18 | 2024-02-27 | 芯潮澎湃生物科技(南京)有限公司 | Co-immune culture organoid chip model |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Nie et al. | Construction of multi-scale vascular chips and modelling of the interaction between tumours and blood vessels | |
| CN103981096B (en) | A kind of two-layer cell culture system organ chip and preparation method thereof | |
| CN112280678B (en) | Detachable and reusable hydrophobic or super-hydrophobic microfluidic organ chip | |
| CN105176816B (en) | A kind of microvascular liver chip and its preparation and application based on cell aggregation | |
| CN111218404A (en) | Bionic multi-organ chip and preparation method and application thereof | |
| CN102124096A (en) | Organ mimic device with microchannels and methods of use and manufacturing thereof | |
| CN116445285A (en) | Organ-like co-culture chip, construction method and co-culture method | |
| CN220166205U (en) | Organ-like co-culture chip | |
| US10030219B2 (en) | Neurovascular unit(NVU)-on-a-chip and method of fabricating the same | |
| Yan et al. | Organ-on-a-chip: A new tool for in vitro research | |
| US20210201702A1 (en) | Use of 3d-printed freestanding structures for ex vivo tissue | |
| JP2017501745A (en) | Fluidic device and perfusion system for the reconstruction of complex biological tissue outside the body | |
| CN109868256A (en) | A kind of kidney organ's chip and kidney organ's drug test model | |
| CN114276930A (en) | Gas-liquid culture type organ chip and application thereof | |
| CN101451105B (en) | Construction method of blood capillary model and microsystem chip thereof | |
| CN109517737A (en) | A kind of micro-fluidic chip and metastasis models and model building method and application based on the chip | |
| CN114540305A (en) | Preparation method of organoid structure based on microfluidic technology high-flux culture | |
| CN108641931A (en) | A kind of digitlization microarray organ chip and its application | |
| Seidi et al. | Simulation and modeling of physiological processes of vital organs in organ-on-a-chip biosystem | |
| CN208762505U (en) | A kind of digitlization microarray organ chip | |
| CN110878285A (en) | Chip organ model for screening bladder tumor chemotherapy drugs and manufacturing method thereof | |
| CN212316139U (en) | Bionic multi-organ chip | |
| CN103396946B (en) | Biological reaction apparatus and its preparation method and application | |
| CN114989977A (en) | Tumor organoid chip for multi-cell interaction and drug screening and preparation method thereof | |
| US20210054319A1 (en) | Flow bioreactor device for monitoring cellular dynamics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| GR01 | Patent grant | ||
| GR01 | Patent grant |