An organ-on-chip model

Abstract

The application relates to the fields of biomedical engineering and microfluidic technology, and particularly relates to an organ-on-chip model, which comprises a substrate, the substrate is provided with cell culture chambers and perfusion channels, the cell culture chambers and the perfusion channels are both provided with a plurality of, the perfusion channels are arranged between the cell culture chambers and are communicated with the cell culture chambers through permeable membranes, the perfusion channels comprise first perfusion channels and second perfusion channels, one end of the first perfusion channels is provided with a first fluid injection hole, the other end is provided with a first fluid collection hole, one end of the second perfusion channels is provided with a second fluid injection hole, the other end is provided with a second fluid collection hole. The organ-on-chip model can be flexibly assembled with different accessories, can meet the culture requirements of different cell sample types, can more truly simulate the influence of drugs or other substances on the physiological functions of organs, and can be used in cell chemotaxis experiments.

Description

Technical Field

[0001] This invention relates to the fields of biomedical engineering and microfluidics, and in particular to an organ-on-a-chip model. Background Technology

[0002] Organ or organ-on-a-chip technology is a specialized chip technology based on 3D cell culture combined with microfluidic systems. It utilizes microfluidics to control fluid flow, combining cell-cell interactions, matrix properties, and biochemical and biomechanical characteristics to simulate and construct a three-dimensional organ physiological microsystem on a chip. Research has found that organ / organ-on-a-chip technology can more accurately and rapidly detect the potential toxicity and efficacy of drugs in humans, reducing the time and economic costs of animal experiments. It will become one of the important tools for drug screening in the future. Simultaneously, this technology also opens new channels for studying the physiological structure, development, and function of organs, laying the foundation for in vitro organ development and culture and organ transplantation technologies.

[0003] The reported designs for liver organ-on-a-chip research mainly focus on simulating the characteristics of a cross-section of hepatocytes and hepatic sinusoids, neglecting the role of bile duct flow and the systemic physiological functions of liver lobules. Although a few studies have mentioned the design of bile ducts in organ-on-a-chips, the chip design is complex, the operation is cumbersome, and 3D cultures are difficult to obtain. Lung organ-on-a-chip designs basically include simulating pulmonary vascular channels and gas flow channels. Moreover, current organ-on-a-chip designs are basically only designed for specific tissues and organs, and can only be applied to the research of specific tissues and organs. They are not compatible with the research applications of other organs / organoids, which greatly limits the scope of application of the chips. Summary of the Invention

[0004] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide an organ-on-a-chip model to solve the problems in the prior art.

[0005] To achieve the above and other related objectives, the present invention provides an organ-on-a-chip model, which includes a substrate on which cell culture chambers and perfusion channels are provided. Multiple cell culture chambers and perfusion channels are provided, with the perfusion channels located between the cell culture chambers and separated from them by a permeable membrane. Each perfusion channel includes a first perfusion channel and a second perfusion channel. The first perfusion channel has a first fluid injection port at one end and a first fluid collection port at the other end. The second perfusion channel has a second fluid injection port at one end and a second fluid collection port at the other end.

[0006] Preferably, the organ-on-a-chip model further includes a filter bed, the shape of which matches the cell culture chamber, the filter bed being fitted inside each cell culture chamber, the filter bed including a connected bottom surface and sidewalls, and at least a portion of the sidewalls being inlaid with a permeable membrane.

[0007] Preferably, a permeable membrane is embedded in the first and second planar sidewalls. The type of permeable membrane is the same as that of the permeable membrane in the adjacent irrigation channel.

[0008] Preferably, the organ-on-a-chip model further includes an isolation frame, which is formed by a second curved sidewall, a third planar sidewall, and a fourth planar sidewall, and the isolation frame is fitted inside the cell culture chamber.

[0009] The present invention also provides the use of the organ-on-a-chip model in drug development, nutritional research, and cell chemotaxis experiments.

[0010] As described above, the organ-on-a-chip model of the present invention has the following beneficial effects: it has two independent perfusion channels, two sets of accessories (filter bed and isolation frame) that can be flexibly matched, and is easy to disassemble and assemble. It can meet the culture requirements of different cell sample types (ultra-low adsorption culture and matrix gel, hydrogel culture methods, etc.), and can more realistically simulate the effects of drugs or other substances on organ physiological functions, including toxicology and nutritional studies. At the same time, it can also meet the requirements of cell chemotaxis experiments, allowing simultaneous study of the effects of multiple chemokines on cell growth and proliferation, and has certain throughput experimental characteristics, enabling real-time observation of cell growth dynamics. Attached Figure Description

[0011] Figure 1 The image shown is a three-dimensional schematic diagram of the organ-on-a-chip model of the present invention.

[0012] Figure 2 The image shown is a top view of the organ-on-a-chip model of the present invention.

[0013] Figure 3 The diagram shown is a three-dimensional schematic of the perfusion channel of the organ-on-a-chip model of the present invention.

[0014] Figures 4-1 to 4-4 The diagram shows a filter bed for an organ-on-a-chip model of the present invention, wherein the diamond and square shaded areas on the sidewalls represent different permeable membranes.

[0015] Figure 5 The diagram shows an isolation frame of the organ-on-a-chip model of the present invention.

[0016] Figure 6 The diagram shows the perfusion direction of the organ-on-a-chip model of the present invention.

[0017] Component designation explanation

[0018] 1. Base

[0019] 11 Cell Culture Chambers

[0020] 111 First Cell Culture Chamber

[0021] 112 Second Cell Culture Chamber

[0022] 113 Third Cell Culture Chamber

[0023] 114 Fourth Cell Culture Chamber

[0024] 12 Irrigation Channels

[0025] 121 First Irrigation Channel

[0026] 122 Second Irrigation Channel

[0027] 123 First fluid injection hole

[0028] 124 First fluid collection hole

[0029] 125 Second fluid injection hole

[0030] 126 Second fluid collection hole

[0031] 2. Filter bed

[0032] 211 Bottom

[0033] 212 Sidewall

[0034] 2121 First curved sidewall

[0035] 2122 First Plane Sidewall

[0036] 2123 Second Plane Sidewall

[0037] 213 Overlap

[0038] 3. Isolation frame

[0039] 31 Second curved sidewall

[0040] 32 Third Plane Sidewall

[0041] 33. Fourth plane sidewall Detailed Implementation

[0042] The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification.

[0043] Please refer to the accompanying drawings. It should be understood that the structures, proportions, sizes, etc., depicted in the accompanying drawings are merely for illustrative purposes to aid those skilled in the art and are not intended to limit the scope of the invention. Therefore, they have no substantial technical significance. Any modifications to the structure, changes in proportions, or adjustments to size, without affecting the effectiveness and purpose of the invention, should still fall within the scope of the disclosed technical content. Furthermore, the terms such as "upper," "lower," "left," "right," "middle," and "one" used in this specification are merely for clarity and are not intended to limit the scope of the invention. Changes or adjustments to their relative relationships, without substantially altering the technical content, should also be considered within the scope of the invention.

[0044] like Figure 1 and 2 As shown, the present invention provides an organ-on-a-chip model, which includes a substrate 1. The substrate 1 is provided with cell culture chambers 11 and perfusion channels 12. Multiple cell culture chambers 11 and multiple perfusion channels 12 are provided. The perfusion channels 12 are located between each cell culture chamber 11 and are separated from the cell culture chambers 11 by a permeable membrane. The perfusion channel 12 includes a first perfusion channel 121 and a second perfusion channel 122. The first perfusion channel 121 is provided with a first fluid injection hole 123 at one end and a first fluid collection hole 124 at the other end. The second perfusion channel 122 is provided with a second fluid injection hole 125 at one end and a second fluid collection hole 126 at the other end.

[0045] The outer contour of the base 1 is rectangular. In one embodiment, the base 1 has a length, width, and height of 5cm × 5cm × 1cm.

[0046] In the present invention, as Figure 2 In the illustrated embodiment, the cell culture chambers 11 are arranged adjacently to form a cylinder. In some embodiments of the invention, the cell culture chambers 11 are of equal size. In one embodiment, there are four cell culture chambers 11: a first cell culture chamber 111, a second cell culture chamber 112, a third cell culture chamber 113, and a fourth cell culture chamber 114. Each cell culture chamber 11 has a quarter-circular cross-section, and the four cell culture chambers 11 are arranged to form a cylinder.

[0047] The bottom of the cell culture chamber 11 can be made of ultra-low adsorption material such as glass, or at least the inner surface is coated with an ultra-low adsorption coating such as a hydrogel coating. It can also be made of materials suitable for cell adhesion growth, such as polystyrene. The bottom thickness is suitable for confocal microscopy observation and imaging.

[0048] The multiple cell culture chambers 11 allow for the addition of different cell types, such as normal hepatocytes, liver cancer cells, or mixed cell cultures, without affecting each other or causing cross-contamination.

[0049] In the present invention, as Figure 3 In the illustrated embodiment, both the first perfusion channel 121 and the second perfusion channel 122 are L-shaped channels. The first perfusion channel 121 and the second perfusion channel 122 are arranged in a cross shape. This arrangement allows the first cell culture chamber 111 and the third cell culture chamber 113 to be perfused from different perfusion channels on both sides, while the second cell culture chamber 112 and the fourth cell culture chamber 114 are perfused from the same perfusion channel on both sides.

[0050] The surfaces of the first perfusion channel 121 and the second perfusion channel 122 adjacent to the cell culture chamber 11 are formed by a permeable membrane. The permeable membrane structure allows fluid in each perfusion channel to permeate into each cell culture chamber 11, or allows metabolites in the cell culture chamber 11 to be discharged into the perfusion channel, and also allows for the exchange of material information between each cell culture chamber 11.

[0051] In one embodiment, the surface of the first perfusion channel 121 adjacent to the cell culture chamber 11 is made of a PDMS (polydimethylsiloxane) membrane. The pore size of the PDMS membrane is selected based on the type and size of the co-cultured cells and the fluid composition. For example, the pore size of the PDMS membrane is 0.1-30 μm. Preferably, the pore size of the PDMS membrane is 1-5 μm.

[0052] In one embodiment, the surface of the second perfusion channel 122 adjacent to the cell culture chamber 11 is made of a PC (polycarbonate) membrane. The pore size of the permeation membrane of the second perfusion channel 122 is, for example, 0.1-30 μm. Preferably, the pore size of the PC membrane is 1-5 μm.

[0053] The first perfusion channel 121 and the second perfusion channel 122 can be used to perfuse different fluids as needed. For example, the two perfusion channels can have the following perfusion modes: culture medium-culture medium, culture medium-gas flow, and gas flow-gas flow. Specifically, in one embodiment, the first perfusion channel 121 is used for culture medium perfusion, and the second perfusion channel 122 is used for bile perfusion.

[0054] During perfusion, the liquid level in each perfusion channel is slightly higher than the liquid level in the cell culture chamber 11, which facilitates the diffusion of molecules in each perfusion channel into the cell culture chamber 11.

[0055] In some embodiments of the present invention, the width of the first perfusion channel 121 is greater than the width of the second perfusion channel 122. The width of the first perfusion channel 121 or the second perfusion channel 122 is 0.1-1 cm. A wider perfusion channel facilitates the formation of a chemokine concentration gradient in cell chemotaxis experiments.

[0056] The bottom surfaces of the first perfusion channel 121 and the second perfusion channel 122 are made of materials suitable for cell adhesion and growth, such as polystyrene, so that cells such as hepatic sinusoidal endothelial cells, bile duct endothelial cells, other non-parenchymal liver cells, and pulmonary vascular endothelial cells can rapidly adhere and proliferate. The thickness of the bottom surfaces of the first perfusion channel 121 and the second perfusion channel 122 is sufficient to meet the requirements for confocal microscopy observation and imaging.

[0057] In the present invention, as Figures 4-1 to 4-4 In the embodiment shown, the organ-on-a-chip model further includes a filter bed 2, the shape of which matches the cell culture chamber 11. The filter bed 2 is fitted inside each cell culture chamber 11. The filter bed 2 includes a bottom surface 211 and a side wall 212 connected to each other, and at least a portion of the side wall 212 is inlaid with a permeable membrane.

[0058] The number of filter beds 2 corresponds to the number of cell culture chambers 11. In one embodiment, four filter beds 2 are provided, which are respectively adapted to the first cell culture chamber 111, the second cell culture chamber 112, the third cell culture chamber 113, and the fourth cell culture chamber 114.

[0059] In some embodiments of the present invention, the cross-section of the filter bed 2 is fan-shaped. Preferably, the central angle of the fan shape is 90 degrees. The sidewall 212 of the filter bed 2 includes a first curved sidewall 2121, a first planar sidewall 2122, and a second planar sidewall 2123 connected in sequence.

[0060] In some embodiments of the present invention, the height of the filter bed 2 is 5 to 10 mm.

[0061] The length of the first planar sidewall 2122 or the second planar sidewall 2123 is 8 to 10 mm.

[0062] like Figure 4-1 As shown, a permeable membrane is embedded in the first planar sidewall 2122 and the second planar sidewall 2123. The type of permeable membrane is the same as that of the permeable membrane in the adjacent irrigation channel. For example... Figure 4-1 and Figure 3As shown, in the filter bed 2 adapted to the first cell culture chamber 111, the permeable membrane embedded in the first planar sidewall 2122 is of the same type as the permeable membrane in the second perfusion channel 122, and the permeable membrane in the second planar sidewall 2123 is of the same type as the permeable membrane in the first perfusion channel 121. For example, in the filter bed 2 adapted to the second cell culture chamber 112, the permeable membranes embedded in both the first planar sidewall 2122 and the second planar sidewall 2123 are of the same type as the permeable membrane in the first perfusion channel 121.

[0063] In one embodiment, the first curved sidewall 2121, the first planar sidewall 2122, and the second planar sidewall 2123 are provided with overlapping edges 213. The overlapping edges 213 facilitate the placement of the filter bed 2 into or removal from the cell culture chamber 11.

[0064] The first curved sidewall 2121 is made of an ultra-low adsorption material or is an ultra-thin structure with an ultra-low adsorption coating. The ultra-low adsorption material is, for example, glass, and the ultra-low adsorption coating is selected from gelatin coatings, hydrogel coatings, or matrix gel coatings. The thickness of the first curved sidewall 2121 is, for example, 0.01–5 mm, preferably 0.1–0.2 mm. The material of the bottom surface 211 is suitable for cell culture methods such as hepatocyte microspheres and small-volume matrix gel 3D culture. It can be an ultra-low adsorption material, such as borosilicate glass (preferably high-transparency borosilicate glass), or a material suitable for cell adhesion growth, such as polystyrene (preferably high-transparency USP class VI polystyrene), as long as the bottom surface material and its thickness are suitable for confocal microscopy.

[0065] In the present invention, as Figure 5 In the embodiment shown, the organ-on-a-chip model further includes an isolation frame 3, which is formed by a second curved sidewall 31, a third planar sidewall 32, and a fourth planar sidewall 33. The isolation frame 3 is attached to the sidewall of the cell culture chamber 11.

[0066] The number of isolation frames 3 corresponds to the number of cell culture chambers 11. In one embodiment, four isolation frames 3 are provided, which are respectively adapted to the first cell culture chamber 111, the second cell culture chamber 112, the third cell culture chamber 113, and the fourth cell culture chamber 114.

[0067] In some embodiments of the present invention, the isolation frame 3 has a fan-shaped cross-section. Preferably, the central angle of the fan shape is 90 degrees.

[0068] The isolation frame 3 is the same as the first curved sidewall 2121, and is also made of ultra-low adsorption material or an ultra-thin structure with an ultra-low adsorption coating. The isolation frame 3 is used to isolate the cell gel suspension to prevent blockage of the perfusion channel, while making the cell culture fit the permeable membrane as closely as possible, and making the gap between the isolation frame 3 and the cell culture chamber 11 as small as possible, so as to be suitable for large-volume flat-lay matrix gel 3D culture. After the gel solidifies, the isolation frame 3 is slowly removed and the perfusion culture is then carried out.

[0069] In some embodiments of the present invention, the organ-on-a-chip model is further provided with a top cover for covering the substrate 1, and the top cover is provided with holes that match the first fluid injection hole 123, the first fluid collection hole 124, the second fluid injection hole 125, and the second fluid collection hole 126.

[0070] In some embodiments of the present invention, the organ-on-a-chip model is further provided with a sealing plug, which is used to seal the first fluid injection port 123, the first fluid collection port 124, the second fluid injection port 125, the second fluid collection port 126, and / or the cell culture chamber 11. The sealing plug is used in cell chemotaxis experiments. The sealing plug is a rubber stopper.

[0071] The first fluid injection port 123, the first fluid collection port 124, the second fluid injection port 125, and the second fluid collection port 126 can be connected to external conduits for use with microfluidics and other power systems.

[0072] The present invention also provides the use of the organ-on-a-chip model in drug development, nutrition and other research.

[0073] Specifically, the intended use refers to its application in studying the interaction between drugs or other substances and organs. The organs are selected from the liver, lungs, and their respective organoids. The organoids are cell clusters established in an in vitro 3D cell induction culture system using primary tissue cells, stem cells, or tumor cells, capable of replicating the complex spatial morphology, location information, and physiological functions of tissues or organs. For example, the interaction between the drugs or other substances and the liver may be studied in areas such as intrahepatic drug metabolism, the liver's influence on drug metabolism, the effects of drugs on liver physiological function, drug toxicology, and nutritional studies.

[0074] When the organ-on-a-chip model of this invention is combined with a microfluidic system, the microfluidic environment of each cell culture chamber is different, making it suitable for culture / co-culture experiments for various research purposes. The method of use for liver organ / organoid on-a-chip is as follows:

[0075] Appropriate amounts of liver sinusoidal endothelial cell suspension and bile duct endothelial cell suspension are injected through the first fluid injection hole 123 and the second fluid injection hole 125, respectively. The organ-on-a-chip model is statically cultured to ensure that the cells in the first perfusion channel 121 and the second perfusion channel 122 adhere to the wall. Then, a filter bed 2 or an isolation frame 3 is placed in the cell culture chamber 11, liver cells and an appropriate amount of culture medium are added, and the chamber is placed in a CO2 incubator for perfusion culture.

[0076] like Figure 6 As shown, the first fluid injection port 123 and the second fluid injection port 125 of the organ-on-a-chip model are connected to a catheter and a power pump. Fresh culture medium and bile are injected from their respective injection ports, flowing through the first perfusion channel 121 and the second perfusion channel 122. The first perfusion channel 121 and the second perfusion channel 122 respectively simulate the physiological structures of hepatic sinusoidal blood flow and bile flow, and the two fluid flows are in opposite directions. Finally, they converge into the first fluid collection port 124 and the second fluid collection port 126, respectively. Each collection port can be connected to a catheter collection tube or a microfluidic power system to collect the fluid, or the fluid can be collected manually. This invention does not specifically limit the composition of the culture medium, the power source of the circulation, or the flow rate.

[0077] The organ-on-a-chip model of the present invention is applied to lung organs / organ-like chips as follows:

[0078] Lung microvascular endothelial cell suspension is injected through the first fluid injection port 123. After standing and adhering to the cell culture wall, a filter bed 2 or isolation frame 3 is placed into the cell culture chamber 11, and lung cells and an appropriate amount of culture medium are added. Finally, gas is introduced through the second fluid injection port 125. The first perfusion channel 121 and the second perfusion channel 122 simulate alveoli and pulmonary vessels, respectively. The cells are then perfused and cultured in a CO2 incubator.

[0079] The method of using the organ-on-a-chip model of the present invention in cell chemotaxis experimental research is as follows:

[0080] Cell suspension was first injected into the first fluid injection port 123 and the second fluid injection port 125. After sealing with a plug, the cells were allowed to stand and adhere evenly to the cell culture wall. Then, chemokine reagent was added to the cell culture chamber 11, and the cell culture chamber 11 was sealed with a plug. The chemokine formed a concentration gradient in the perfusion channel. The chamber was then placed in a CO2 incubator for perfusion culture. Cell growth in the perfusion channel was observed in real time, and images were taken for ImageJ data analysis. Multiple cell culture chambers 11 and multiple perfusion channels can simultaneously meet the needs of studying the effects of multiple chemokines on cell growth and proliferation, providing a certain throughput experimental capability.

[0081] In summary, the organ-on-a-chip model of this invention: 1) can be applied to liver organ-on-a-chip research, adding sinusoidal fluid and bile fluid flow systems, enabling co-culture of other non-parenchymal liver cells such as sinusoidal endothelial cells and bile duct endothelial cells, further improving the cell culture system for liver lobules in vitro organ-on-a-chip; 2) can be applied to lung organ / organoid-on-a-chip research, realizing the organ physiological structure simulating alveoli and pulmonary vessels; 3) all fluid flow systems and culture chambers can be recovered and detected; 4) can be applied to cell chemotaxis experiments, and can simultaneously meet the needs of studying the effects of multiple chemokines on cell growth and proliferation, possessing certain throughput experimental characteristics; 5) the chip has a simple structure, is easy to operate, has a wide range of applications, and can be flexibly assembled and disassembled to meet the different needs of 3D culture methods (ultra-low adsorption culture and matrix gel, hydrogel culture methods, etc.); 6) 3D cultures can be easily recovered for downstream detection and observation. Therefore, this invention effectively overcomes the various shortcomings of existing technologies and has high industrial application value.

[0082] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. An organ-on-a-chip model, characterized in that, The organ-on-a-chip model includes a substrate (1), on which cell culture chambers (11) and perfusion channels (12) are provided. Multiple cell culture chambers (11) and perfusion channels (12) are provided. The perfusion channels (12) are located between the cell culture chambers (11) and separated from them by a permeable membrane. Each perfusion channel (12) includes a first perfusion channel (121) and a second perfusion channel (122). One end of the first perfusion channel (121) has a first fluid injection port (123), and the other end has a first fluid collection port (124). The second perfusion channel (122) has a second fluid injection hole (125) at one end and a second fluid collection hole (126) at the other end; the cell culture chamber (11) has four chambers, namely the first cell culture chamber (111), the second cell culture chamber (112), the third cell culture chamber (113), and the fourth cell culture chamber (114), which are arranged adjacently to form a cylinder; the first perfusion channel (121) and the second perfusion channel (122) are both L-shaped; the first perfusion channel (121) and the second perfusion channel (122) are arranged in a cross shape.

2. The organ-on-a-chip model according to claim 1, characterized in that, The bottom surface of the cell culture chamber (11) is made of polystyrene or borosilicate glass; or, the bottom surface of the cell culture chamber (11) is provided with one or more of the following: hydrogel coating, gelatin coating, and matrix adhesive coating.

3. The organ-on-a-chip model according to claim 1, characterized in that, The surface of the first perfusion channel (121) adjacent to the cell culture chamber (11) is made of PDMS membrane.

4. The organ-on-a-chip model according to claim 1, characterized in that, The surface of the second perfusion channel (122) adjacent to the cell culture chamber (11) is made of PC membrane.

5. The organ-on-a-chip model according to claim 1, characterized in that, The bottom material of the first irrigation channel (121) or the second irrigation channel (122) is selected from polystyrene or borosilicate glass.

6. The organ-on-a-chip model according to claim 1, characterized in that, The width of the first irrigation channel (121) is greater than the width of the second irrigation channel (122).

7. The organ-on-a-chip model according to claim 1, characterized in that, The organ-on-a-chip model also includes a filter bed (2), which is fitted inside each cell culture chamber (11). The filter bed (2) includes a bottom surface (211) and a side wall (212) connected to each other, and at least part of the side wall (212) is inlaid with a permeable membrane.

8. The organ-on-a-chip model according to claim 7, characterized in that, The number of filter beds (2) is matched with the number of cell culture chambers (11).

9. The organ-on-a-chip model according to claim 8, characterized in that, The filter bed (2) is provided in four parts, which are respectively adapted to the first cell culture chamber (111), the second cell culture chamber (112), the third cell culture chamber (113), and the fourth cell culture chamber (114).

10. The organ-on-a-chip model according to claim 7, characterized in that, The sidewall (212) of the filter bed includes a first curved sidewall (2121), a first planar sidewall (2122), and a second planar sidewall (2123) connected in sequence; the thickness of the bottom surface (211) is 0.01~5mm.

11. The organ-on-a-chip model according to claim 10, characterized in that, The material of the first curved sidewall (2121) is glass, or the first curved sidewall (2121) has a hydrogel coating, gelatin coating or matrix adhesive coating on at least the inner surface.

12. The organ-on-a-chip model according to claim 10, characterized in that, The first planar sidewall (2122) and the second planar sidewall (2123) are inlaid with permeable membranes.

13. The organ-on-a-chip model according to claim 12, characterized in that, The type of permeable membrane embedded on the first planar sidewall (2122) and the second planar sidewall (2123) is the same as the type of permeable membrane in the adjacent irrigation channel.

14. The organ-on-a-chip model according to claim 10, characterized in that, The thickness of the first curved sidewall (2121) is 0.01~5mm.

15. The organ-on-a-chip model according to claim 10, characterized in that, The material of the bottom surface (211) is selected from polystyrene or borosilicate glass.

16. The organ-on-a-chip model according to claim 10, characterized in that, The first curved sidewall (2121), the first planar sidewall (2122) and / or the second planar sidewall (2123) are provided with an overlap (213).

17. The organ-on-a-chip model according to claim 1, characterized in that, The organ-on-a-chip model also includes an isolation frame (3), which is formed by a second curved sidewall (31), a third planar sidewall (32), and a fourth planar sidewall (33). The isolation frame (3) is attached to the sidewall of the cell culture chamber (11).

18. The organ-on-a-chip model according to claim 17, characterized in that, The number of isolation frames (3) is matched with the number of cell culture chambers (11).

19. The organ-on-a-chip model according to claim 18, characterized in that, The isolation frame (3) is provided in four parts, which are respectively adapted to the first cell culture chamber (111), the second cell culture chamber (112), the third cell culture chamber (113), and the fourth cell culture chamber (114).

20. The organ-on-a-chip model according to claim 17, characterized in that, The isolation frame (3) is made of glass, or the isolation frame (3) has at least a hydrogel coating, gelatin coating or matrix adhesive coating on its inner surface; the thickness of the isolation frame (3) is 0.01~5mm.

21. The organ-on-a-chip model according to claim 1, characterized in that, The organ-on-a-chip model is also provided with a top cover, which is used to cover the substrate (1).

22. The organ-on-a-chip model according to claim 21, characterized in that, The top cover is provided with holes that match the first fluid injection hole (123), the first fluid collection hole (124), the second fluid injection hole (125), and the second fluid collection hole (126).

23. The organ-on-a-chip model according to claim 1, characterized in that, The organ-on-a-chip model is also provided with a sealing plug, which is used to seal the first fluid injection hole (123), the first fluid collection hole (124), the second fluid injection hole (125), the second fluid collection hole (126) and / or the cell culture chamber (11).

24. The use of the organ-on-a-chip model according to any one of claims 1-23 in drug development, nutritional research, and cell chemotaxis experiments.

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