Organ-like chip and preparation method and application thereof

Abstract

The invention relates to the technical field of organ-like chips, in particular to an organ-like chip and a preparation method and application thereof.The organ-like chip comprises a first culture base and a second culture base, a first cover plate is detachably installed on the upper surface of the first culture base, and a second cover plate is detachably installed on the upper surface of the second culture base; culture grooves are formed in the upper surfaces of the first culture base and the second culture base, and a flowing channel is arranged between the culture grooves. One culture base can serve as an independent organ simulation unit, communication of a plurality of culture bases can be conveniently achieved through connection of the communicating pipe and the liquid outlet pipe, and then biological connection and interaction among multiple organs are simulated; therefore, researchers can flexibly combine different organs according to research requirements to construct a multi-organ model closer to the physiological environment of a human body.

Description

Technical Field

[0001] The present invention relates to the technical field of organ-on-a-chip, and in particular to an organ-on-a-chip, a preparation method thereof, and an application thereof. Background Art

[0002] An organ-on-a-chip is a microfluidic device that can simulate the functions of human organs and create an environment similar to that inside the human body, and is used for disease research, new drug discovery and testing, and exploration of personalized treatment methods. With the continuous progress of technology, organ-on-a-chip has gradually moved towards the core position of R & D and testing, promising to revolutionize the field of pharmaceutical R & D, providing more accurate data than animal models, and possibly solving the problem of health inequality while reducing the need for animal experiments.

[0003] The published patent No. CN114015568B discloses an organ-on-a-chip, including a chip cartridge body. The chip cartridge body is sequentially provided with a first layer for culturing cells, a second layer for blocking, a third layer for material exchange, and a fourth layer for culturing cells from top to bottom; the first layer includes a first substrate, and multiple groups of first culture regions are arranged on the first substrate. The first culture regions are provided with a first cell culture chamber, a second cell culture chamber, a third cell culture chamber, and a fourth cell culture chamber that are sequentially arranged and connected, and a fifth cell culture chamber, a sixth cell culture chamber, a seventh cell culture chamber, and an eighth cell culture chamber that are sequentially arranged and connected, which can culture various types of cells, is beneficial to miniaturization and integration, and is easy to clean.

[0004] After the existing organ-on-a-chip simulates an organ, it is an independent chip, that is, an independent organ. In simulation experiments, multiple organs are often required for simulation. A single chip cannot be connected to other chips, and multiple organs cannot be connected. Therefore, we propose an organ-on-a-chip that can achieve multi-organ simulation. Summary of the Invention

[0005] To achieve the above object, the present invention provides an organ-on-a-chip, including a first culture base and a second culture base. A first cover plate is detachably installed on the upper surface of the first culture base, and a second cover plate is detachably installed on the upper surface of the second culture base. Culture grooves are formed on the upper surfaces of the first culture base and the second culture base, and a flow channel is arranged between the culture grooves; The upper surface of the first cover plate is provided with a liquid injection pipe communicating with the inside of the culture tank. The lower surface of the first culture medium seat is provided with a liquid outlet pipe communicating with the inside of the culture tank. A filter screen is installed inside the culture tank where the liquid outlet pipe is installed. The upper surface of the second cover plate is provided with a communicating pipe communicating with the inside of the culture tank. A rubber ring is fixedly connected to the surface of the liquid outlet pipe. An annular groove is formed on the surface of the liquid outlet pipe. The inner ring surface of the rubber ring is fixedly connected to the inner wall of the annular groove. The diameter of the rubber ring is adapted to the inner diameter of the communicating pipe. The liquid outlet pipe is inserted into the communicating pipe. A connecting mechanism is installed between the first culture medium seat and the second cover plate.

[0006] In one example, connecting seats are fixedly connected to the lower surfaces of the first cover plate and the second cover plate. Installation grooves are formed on the upper surfaces of the first culture medium seat and the second culture medium seat. The connecting seats are located inside the installation grooves, and the surfaces of the connecting seats are lapped with the inner walls of the installation grooves.

[0007] In one example, a T-shaped groove is formed on the side surface of the connecting seat. A T-shaped positioning block is slidably connected to the inner wall of the T-shaped groove. A connecting spring is fixedly connected between the opposite surfaces of the T-shaped positioning block and the T-shaped groove. A positioning port is formed on the inner wall of the installation groove. The surface of the T-shaped positioning block is lapped with the inner wall of the positioning port.

[0008] In one example, the T-shaped positioning block is located inside the positioning port. The lower surface of the T-shaped positioning block is arc-shaped, and the lower surface of the T-shaped positioning block is semi-arc-shaped.

[0009] In one example, the connecting mechanism includes connecting support feet. The connecting support feet are fixedly installed at the four corners of the lower surface of the first culture medium seat. An installation sleeve is fixedly connected to the upper surface of the second cover plate. The connecting support feet are inserted into the inside of the installation sleeve.

[0010] In one example, a T-shaped groove is formed on the surface of the connecting support foot. A T-shaped positioning rod is slidably connected to the inner wall of the T-shaped groove. A return spring is fixedly connected between the opposite surfaces of the T-shaped positioning rod and the T-shaped groove.

[0011] In one example, the end face of the T-shaped positioning rod is hemispherical. An arc-shaped groove is formed on the inner wall of the installation sleeve. The end face of the T-shaped positioning rod is lapped with the inner wall of the arc-shaped groove.

[0012] In one example, it includes the following steps: Step 1: Preparation for production. Select polydimethylsiloxane as the base material of the organoid chip. Use computer-aided design software to design the layout of the chip. Prepare processing equipment and related chemical reagents. Step 2: Grooving production. Use a lithography machine to groove the base, including cleaning and coating with glue, exposure, development, etching, and removing the photoresist. Step 3: Fabrication of the flow channel. Design a three-dimensional model of the microfluidic flow channel, and perform photolithography on the substrate material to form the mold pattern of the microfluidic flow channel. Step 4: Drilling and grooving. Drill holes at the positions where connection to other components is required, then insert the corresponding pipes or connectors into the holes, and fix and seal them by bonding. Step 5: Fabrication of the connectors. Use a machine tool to fabricate and assemble the connection base, connection support feet, mounting sleeves, T-shaped positioning blocks, and T-shaped positioning rods, and connect the connectors to the base by bonding.

[0013] In one example, the organoid chip is used in the fields of disease model construction, drug screening, and precision medicine.

[0014] The organoid chip, its preparation method, and application proposed by the present invention can bring the following beneficial effects: 1. In the present invention, one culture medium base can serve as an independent organ simulation unit. Through the connection of the communication pipe and the liquid outlet pipe, the communication of multiple culture medium bases can be conveniently achieved, thereby simulating the biological connection and interaction between multiple organs. This modular design enables researchers to flexibly combine different "organs" according to research needs to construct a multi-organ model closer to the human physiological environment, which helps to deeply explore complex physiological and pathological processes such as signal transmission between organs, material exchange, and the spread mechanism of diseases between multiple organs, provides a more comprehensive and accurate in vitro simulation platform for medical research, promotes the development of work such as disease mechanism research and drug development, and has broader applicability and deeper research potential compared with traditional single-organ simulation methods.

[0015] 2. In the present invention, the first cover plate and the second cover plate are fixed to the corresponding culture medium base through a unique connection base and T-shaped positioning block structure. During installation, when the T-shaped positioning block is forced to squeeze and retract the spring and moves to the position of the positioning port, the spring elasticity makes it automatically insert into the positioning port to complete the fixation; during disassembly, press the T-shaped positioning block to move the arc surface to the positioning port, and then pull it upward to complete the disassembly. This design makes the disassembly and assembly of the cover plate very convenient and efficient, without the need for complex tools or cumbersome operation steps. During the use of the organoid chip, it is convenient for researchers to regularly clean, disinfect, or replace the culture medium and other internal structures, effectively ensuring the cleanliness of the internal environment of the chip and the stability of the culture conditions, which helps to improve the success rate of organoid culture and the accuracy of experimental results, and at the same time reduces the use cost and maintenance difficulty of the chip, enhancing its practicality and economy in actual applications. Description of the Drawings

[0016] The accompanying drawings described herein are used to provide a further understanding of the present invention and form a part of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation to the present invention. In the drawings: Figure 1 It is a schematic three-dimensional structure diagram of a kind of organoid chip of the present invention; Figure 2 It is a schematic structure diagram of the first culture medium base of a kind of organoid chip of the present invention; Figure 3 It is a schematic internal structure diagram of the first culture medium base of a kind of organoid chip of the present invention; Figure 4 It is a schematic internal structure diagram of the connecting pipe of a kind of organoid chip of the present invention; Figure 5 It is a schematic internal structure diagram of the connecting support feet of a kind of organoid chip of the present invention.

[0017] The reference numerals are as follows: 1 First culture medium base, 2 Second culture medium base, 3 First cover plate, 4 Second cover plate, 5 Connecting seat, 6 T-shaped positioning block, 7 Connecting spring, 8 Culture tank, 9 Flow channel, 10 Liquid injection pipe, 11 Liquid outlet pipe, 12 Filter screen, 13 Connecting pipe, 14 Connecting support feet, 15 Mounting sleeve, 16 T-shaped positioning rod, 17 Return spring. Detailed implementation manners

[0018] In order to more clearly illustrate the overall concept of the present invention, the following will be described in detail by way of examples in conjunction with the drawings of the specification.

[0019] In the description of the present invention, it should be understood that the orientation or positional relationship indicated by the terms "center", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "axial", "radial", "circumferential", etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation to the present invention.

[0020] In addition, the terms "first" and "second" are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. In the description of the present invention, "a plurality" means two or more unless otherwise specifically defined.

[0021] In the present invention, unless otherwise clearly defined or limited, terms such as "installed", "connected", "linked", "fixed", etc. shall be understood in a broad sense. For example, it may be a fixed connection, a detachable connection, or integrated; it may be a mechanical connection, an electrical connection, or a communication connection; it may be directly connected, or indirectly connected through an intermediate medium, and it may be the internal communication of two components or the interaction relationship between two components. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0022] In the present invention, unless otherwise clearly defined or limited, the first feature being "on" or "under" the second feature may be that the first and second features are in direct contact, or the first and second features are indirectly in contact through an intermediate medium. In the description of this specification, the description with reference to terms such as "one solution", "some solutions", "example", "specific example", or "some examples", etc. means that the specific features, structures, materials, or characteristics described in connection with the solution or example are included in at least one solution or example of the present invention. In this specification, the schematic expressions of the above terms do not necessarily refer to the same solution or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more solutions or examples.

[0023] As Figures 1 to 5 shown, the present invention provides an organoid chip and its preparation method and application, including a first culture medium base 1 and a second culture medium base 2. The upper surface of the first culture medium base 1 is covered with a first cover plate 3, and the upper surface of the second culture medium base 2 is covered with a second cover plate 4. To ensure the fixation of the first cover plate 3 and the second cover plate 4 on the first culture medium base 1 and the second culture medium base 2 respectively, connection seats 5 are fixedly connected to the lower surfaces of the first cover plate 3 and the second cover plate 4. Installation grooves are provided on the upper surfaces of the first culture medium base 1 and the second culture medium base 2. The connection seats 5 are located inside the installation grooves, and the surface of the connection seats 5 abuts against the inner wall of the installation grooves.

[0024] A T-shaped groove is provided on the side surface of the connection seat 5. A T-shaped positioning block 6 is slidably connected to the inner wall of the T-shaped groove. A connection spring 7 is fixedly connected to the opposite surface of the T-shaped positioning block 6 and the T-shaped groove. A positioning port is provided on the inner wall of the installation groove. The surface of the T-shaped positioning block 6 abuts against the inner wall of the positioning port. The T-shaped positioning block 6 is located inside the positioning port. At this time, the fixation of the connection seat 5 inside the installation groove is completed, thereby completing the connection between the first cover plate 3 and the first culture medium base 1 and the connection between the second cover plate 4 and the second culture medium base 2.

[0025] To facilitate the insertion of the connecting seat 5 into the installation groove, the lower surface of the T-shaped positioning block 6 is designed to be arc-shaped. When placing the connecting seat 5, the lower arc surface of the T-shaped positioning block 6 is stressed. At this time, the T-shaped positioning block 6 will be subjected to a force pushing it into the T-shaped groove. The T-shaped positioning block 6 squeezes the connecting spring 7 and is received in the T-shaped groove. When the T-shaped positioning block 6 moves to the position of the positioning port, the elastic force of the connecting spring 7 will actively push the T-shaped positioning block 6 into the positioning port. To facilitate the detachment of the T-shaped positioning block 6 from the positioning port, the upper surface of the T-shaped positioning block 6 is designed to be semi-arc-shaped, that is, the upper surface of the T-shaped positioning block 6 is composed of an arc surface and a plane. When the T-shaped positioning block 6 is normally inserted into the positioning port, the plane on the upper surface of the T-shaped positioning block 6 abuts against the inner top wall of the positioning port. At this time, when pulling up the connecting seat 5, the plane can block it to prevent the movement of the connecting seat 5 and ensure stable connection. When it is necessary to remove the connecting seat 5, press the T-shaped positioning block 6 to move the arc surface on the upper surface of the T-shaped positioning block 6 to the positioning port. At this time, pull up the connecting seat 5, and the upper arc surface of the T-shaped positioning block 6 will be stressed. Similarly, it is received in the T-shaped groove, and the disassembly of the connecting seat 5 can be completed, thus facilitating the disassembly of the first cover plate 3 and the second cover plate 4 on the first culture medium seat 1 and the second culture medium seat 2 respectively.

[0026] Culture grooves 8 are provided on the upper surfaces of both the first culture medium seat 1 and the second culture medium seat 2, and a flow channel 9 is provided between the culture grooves 8. To prevent fluid from flowing out due to the sealing after the first cover plate 3 and the second cover plate 4 are installed on the first culture medium seat 1 and the second culture medium seat 2, rubber pads are installed around the flow channel 9 and the culture grooves 8, and the rubber pads play a sealing role.

[0027] A liquid injection tube 10 communicating with the inside of the culture groove 8 is installed on the upper surface of the first cover plate 3. An outlet tube 11 communicating with the inside of the culture groove 8 is provided on the lower surface of the first culture medium seat 1. A filter net 12 is installed inside the culture groove 8 where the outlet tube 11 is installed. The filter net 12 is used for filtering cells and can play a blocking role to simulate the unique cells in the organ. A communicating tube 13 communicating with the inside of the culture groove 8 is installed on the upper surface of the second cover plate 4. Through the connection between the communicating tube 13 and the outlet tube 11, the connection between the first culture medium seat 1 and the second culture medium seat 2 can be realized, and then the biological connection between the organs can be simulated. To prevent a gap from appearing between the communicating tube 13 and the outlet tube 11, a rubber ring is fixedly connected to the surface of the outlet tube 11. An annular groove is provided on the surface of the outlet tube 11. The inner ring surface of the rubber ring is fixedly connected to the inner wall of the annular groove. The diameter of the rubber ring is adapted to the inner diameter of the communicating tube 13. When the outlet tube 11 is inserted into the communicating tube 13, the rubber ring fits against the inner wall of the communicating tube 13 to ensure sealing.

[0028] To ensure the stability after the first culture medium base 1 is connected to the second culture medium base 2, a connecting support foot 14 is fixedly connected to the lower surface of the first culture medium base 1, and a mounting sleeve 15 is fixedly connected to the upper surface of the second cover plate 4. The connecting support foot 14 is located inside the mounting sleeve 15. The number of connecting support feet 14 is four, and the four connecting support feet 14 are respectively located at the four corners of the lower surface of the first culture medium base 1. A T-shaped groove is formed on the surface of the connecting support foot 14, and a T-shaped positioning rod 16 is slidably connected to the inner wall of the T-shaped groove. A return spring 17 is fixedly connected to the opposite surfaces of the T-shaped positioning rod 16 and the T-shaped groove. The end face of the T-shaped positioning rod 16 is hemispherical, and an arc-shaped groove is formed on the inner wall of the mounting sleeve 15. The end face of the T-shaped positioning rod 16 abuts against the inner wall of the arc-shaped groove.

[0029] When the first culture medium base 1 is placed on the second culture medium base 2, the connecting support foot 14 is inserted into the mounting sleeve 15. At this time, the hemispherical surface of the T-shaped positioning rod 16 is forced to be received, and the T-shaped positioning rod 16 is received in the T-shaped groove. When the T-shaped positioning rod 16 moves to the arc-shaped groove, the T-shaped positioning rod 16 is pushed by the elastic force of the return spring 17 and inserted into the arc-shaped groove to complete the connection between the first culture medium base 1 and the second culture medium base 2. And when the second culture medium base 2 is fixed and the first culture medium base 1 is lifted, the hemispherical surface of the T-shaped positioning rod 16 will also be received, completing the separation of the first culture medium base 1 and the second culture medium base 2.

[0030] The preparation method of the above organoid chip includes the following steps: Step 1: Preparation for production. Polydimethylsiloxane is selected as the base material of the organoid chip, which has good biocompatibility and transparency and is suitable for microfluidic applications. According to the structural and functional characteristics of the organ or tissue to be simulated, a computer-aided design software is used to design the layout of the chip, including the shape, size, position, etc. of the culture tank 8 and the flow channel 9. Prepare equipment such as a lithography machine, a soft lithography mold, a 3D printer, a laser cutting machine, etc., as well as relevant chemical reagents, cell culture utensils, etc.; Step 2: Grooving production. Grooving is carried out using a lithography machine, including cleaning and coating: the base material is cleaned and then coated with photoresist, exposure: the mask plate is placed on the base material, and the lithography machine is used for exposure to cause a chemical reaction in the exposed area of the photoresist, development: the exposed base material is put into the developer, and the unexposed photoresist will be dissolved to form the pattern of the groove, etching: the etching technology is used to remove the area not covered by the photoresist to form the actual groove, and removing the photoresist: the remaining photoresist is removed by using methods such as solvent or plasma cleaning to obtain a clean groove structure; Step 3: Fabrication of the flow channel 9. Use CAD software to design a 3D model of the microfluidic flow channel 9, including parameters such as the starting point, ending point, branches, width, and depth of the flow channel 9. Perform photolithography on the substrate material to form a mold pattern of the microfluidic flow channel 9. For PDMS material, pour the PDMS prepolymer on the mold and obtain a chip with the microfluidic flow channel 9 after curing. Other materials such as PMMA can also be used, and the flow channel 9 can be fabricated by methods such as injection molding or hot pressing. Bond the fabricated chip with the flow channel 9 to a cover glass or other substrate material to form a closed microfluidic flow channel 9. Depending on the materials, the bonding method can be selected from plasma treatment, chemical adhesives, etc.

[0031] Step 4: Drilling and grooving. Drill holes at the positions where connections are needed with other components such as the culture tank 8, liquid injection tube 10, liquid outlet tube 11, etc. Then insert the corresponding pipes or connectors into the holes and fix and seal them by means such as bonding, welding, or interference fit.

[0032] Step 5: Fabrication of the connectors. Use a machine tool to fabricate and assemble the connection base 5, connection support feet 14, mounting sleeve 15, T-shaped positioning block 6, and T-shaped positioning rod 16, and connect the connectors to the base by bonding.

[0033] Each embodiment in this specification is described in a progressive manner. For the same or similar parts among the embodiments, reference can be made to each other. Each embodiment focuses on the differences from other embodiments. In particular, for the system embodiment, since it is basically similar to the method embodiment, the description is relatively simple, and reference can be made to the relevant part of the method embodiment for the related content.

[0034] The above description is only for the embodiments of the present invention and is not intended to limit the present invention. For those skilled in the art, various modifications and changes can be made to the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the scope of the claims of the present invention.

Claims

1. An organoid chip, comprising a first culture medium base (1) and a second culture medium base (2), characterized in that: The upper surface of the first culture medium base (1) is detachably installed with a first cover plate (3), the upper surface of the second culture medium base (2) is detachably installed with a second cover plate (4), culture grooves (8) are provided on the upper surfaces of the first culture medium base (1) and the second culture medium base (2), and a flow channel (9) is arranged between the culture grooves (8); A liquid injection pipe (10) communicated with the inside of the culture groove (8) is installed on the upper surface of the first cover plate (3), a liquid outlet pipe (11) communicated with the inside of the culture groove (8) is provided on the lower surface of the first culture medium base (1), a filter net (12) is installed inside the culture groove (8) where the liquid outlet pipe (11) is installed, a communicating pipe (13) communicated with the inside of the culture groove (8) is installed on the upper surface of the second cover plate (4), a rubber ring is fixedly connected to the surface of the liquid outlet pipe (11), an annular groove is provided on the surface of the liquid outlet pipe (11), the inner ring surface of the rubber ring is fixedly connected to the inner wall of the annular groove, the diameter of the rubber ring is adapted to the inner diameter of the communicating pipe (13), the liquid outlet pipe (11) is inserted into the communicating pipe (13), and a connecting mechanism is installed between the first culture medium base (1) and the second cover plate (4).

2. The organoid chip according to claim 1, wherein: Connecting seats (5) are fixedly connected to the lower surfaces of the first cover plate (3) and the second cover plate (4), installation grooves are provided on the upper surfaces of the first culture medium base (1) and the second culture medium base (2), the connecting seats (5) are located inside the installation grooves, and the surface of the connecting seat (5) is lapped with the inner wall of the installation groove.

3. The organoid chip according to claim 2, characterized in that: A T-shaped groove is provided on the side surface of the connecting seat (5), a T-shaped positioning block (6) is slidably connected to the inner wall of the T-shaped groove, a connecting spring (7) is fixedly connected between the opposite surfaces of the T-shaped positioning block (6) and the T-shaped groove, a positioning port is provided on the inner wall of the installation groove, and the surface of the T-shaped positioning block (6) is lapped with the inner wall of the positioning port.

4. The organoid chip according to claim 3, wherein: The T-shaped positioning block (6) is located inside the positioning port, the lower surface of the T-shaped positioning block (6) is arc-shaped, and the lower surface of the T-shaped positioning block (6) is semi-arc-shaped.

5. The organoid chip according to claim 1, characterized in that: The connecting mechanism includes connecting support feet (14), the connecting support feet (14) are fixedly installed at the four corners of the lower surface of the first culture medium base (1), an installation sleeve (15) is fixedly connected to the upper surface of the second cover plate (4), and the connecting support feet (14) are inserted into the inside of the installation sleeve (15).

6. The organoid chip according to claim 5, characterized in that: A T-shaped groove is provided on the surface of the connecting support foot (14), a T-shaped positioning rod (16) is slidably connected to the inner wall of the T-shaped groove, and a return spring (17) is fixedly connected between the opposite surfaces of the T-shaped positioning rod (16) and the T-shaped groove.

7. The organoid chip according to claim 6, characterized in that: The end face of the T-shaped positioning rod (16) is hemispherical, an arc-shaped groove is provided on the inner wall of the installation sleeve (15), and the end face of the T-shaped positioning rod (16) is lapped with the inner wall of the arc-shaped groove.

8. A preparation method for manufacturing an organoid chip according to any one of claims 1 to 7, characterized in that: It includes the following steps: Step 1: Production preparation, select polydimethylsiloxane as the base material of the organoid chip, use computer-aided design software to design the layout of the chip, and prepare processing equipment and related chemical reagents; Step 2: Grooving production, use a lithography machine to groove the base, including cleaning and coating, exposure, development, etching, and removing photoresist; Step 3: Fabrication of the flow channel (9). Design a three-dimensional model of the microfluidic flow channel (9), and perform photolithography on the substrate material to form a mold pattern of the microfluidic flow channel (9). Step 4: Grooving and drilling. Drill holes at the positions where connections to other components are required, then insert the corresponding pipes or connectors into the holes, and fix and seal them by bonding. Step 5: Fabrication of connectors. Use a machine tool to fabricate and assemble the connection base (5), connection support feet (14), mounting sleeve (15), T-shaped positioning block (6), and T-shaped positioning rod (16), and connect the connectors to the base by bonding.

9. Application of an organoid chip, characterized in that: The organoid chip according to any one of claims 1 to 7 is used in the fields of disease model construction, drug screening, and precision medicine.

Images