Biochip structure for co-culture of cells

Abstract

The utility model provides a biochip structure for cell co-culture, which comprises an upper layer plate and a lower layer plate which are stacked, the upper layer plate is provided with a liquid inlet and a liquid outlet, at least two culture cavities are arranged between the liquid inlet and the liquid outlet, the lower layer plate comprises a connection channel, the liquid inlet and the liquid outlet are communicated through the connection channel, and the liquid inlet and the liquid outlet are communicated through the connection channel. A porous membrane is further arranged between the upper layer plate and the lower layer plate, the porous membrane covers the lower end of each culture cavity, the culture problem of highly bionic liver tissue and skin tissue is solved, and a skin-liver dynamic micro-physiological system is built.

Description

Technical Field

[0001] The utility model relates to the field of cell culture, in particular to a biochip structure used for combined cell culture. Background Art

[0002] Drug-induced hepatotoxicity and liver damage are the main causes of acute liver failure and have become a major health issue. Drug hepatotoxicity is also one of the main reasons for the failure of drug clinical trials. Currently, drug hepatotoxicity is usually evaluated in animal models, which often cannot accurately predict clinical responses due to species differences with humans. Therefore, it is of great significance to develop an accurate and effective model to evaluate drug hepatotoxicity.

[0003] With the development of microfluidics, microfabrication, tissue engineering and other technologies, organ chips have become one of the best tools for large-scale drug testing. Organ chips simulate the organ functions in the human body in vitro, have a high degree of biomimetic and a precisely controllable microenvironment, and significantly improve the ability to predict drug responses. Clinically, systemic administration (oral, injection) and local transdermal administration are both common methods of administration. There are differences in liver toxicity caused by different administration methods, which need to be carefully evaluated. In addition, drug-induced adverse skin reactions are common worldwide, often caused by oral or intravenous drugs entering the systemic circulation. The system of two organs, the liver and the skin, provides a more accurate (i.e., including the upstream reactions of liver metabolism) research method for the study of drug-induced adverse skin reactions. Therefore, in order to realize the evaluation of drug hepatotoxicity under systemic administration and local transdermal administration on organ chips, as well as the adverse skin reactions caused by drug metabolism by the liver, it is necessary to simultaneously construct highly biomimetic liver tissue and skin tissue on a chip to improve the systematicness and accuracy of drug testing. Utility Model Content

[0004] The utility model provides a biochip structure for combined cell culture, which solves the problem of combined culture of highly bionic liver tissue and skin tissue.

[0005] In order to solve the above technical problems, the technical solution adopted by the utility model is: a biochip structure for cell co-culture, including a stacked upper plate and a lower plate, the upper plate is provided with a liquid inlet and a liquid outlet, at least two culture chambers are provided between the liquid inlet and the liquid outlet, the lower plate includes a connecting groove, the liquid inlet and the liquid outlet are connected through the connecting groove, the lower end of each culture chamber is connected to the connecting groove, and a porous membrane is also provided between the upper plate and the lower plate, and the porous membrane covers the lower end of each culture chamber.

[0006] In a preferred embodiment, a first sealing pad and a second sealing pad are respectively provided on the upper and lower sides of the porous membrane, the upper plate and the lower plate are closed and clamped to clamp the porous membrane, a plurality of second through holes are provided on the first sealing pad, each second through hole is aligned with each culture chamber, a through waist groove is provided on the second sealing pad, and a first through hole and a third through hole are also provided on the first sealing pad and the second sealing pad, and the first through hole and the third through hole are respectively aligned with the liquid inlet and the liquid outlet.

[0007] In a preferred solution, a sinking groove is provided at the through waist groove, and the porous membrane is placed in the sinking groove.

[0008] In a preferred solution, a plurality of top columns are provided in the connecting channel, a flow channel is provided at the upper end of the top column, and the upper end of the top column abuts against the lower end of the porous membrane.

[0009] In the preferred solution, the top column is provided with multiple rows, and a plurality of rotatable adjustment columns arranged in a straight line are provided in the center of the connecting groove. The adjustment column is provided with a strip baffle, and a rotating shaft is provided at one end of the adjustment column. The rotating shaft is rotatably connected to the lower plate and passes through the lower plate. An annular groove is provided at the end of the rotating shaft, and a plurality of disc springs are also provided. The disc spring is provided with a U-shaped groove, and a clamping portion is provided at the bottom end of the U-shaped groove. The clamping portion is clamped with the annular groove, and the outer edge of the disc spring rests against the bottom end of the lower plate.

[0010] In a preferred embodiment, the pore size of the porous membrane is 0.4-1 μm.

[0011] The beneficial effects of the utility model are as follows: by constructing a culture environment similar to blood flow and adopting at least two culture chambers, skin tissue and liver tissue can be cultured at the same time, which is used to study the hepatotoxicity evaluation of drugs under systemic administration and local transdermal administration, and can also be used to study the skin adverse reactions caused by drug metabolism through the liver; the detachable structure is adopted, the processing difficulty is low, the assembly is easy, and the reusability is high; the layers are easy to disassemble, which is convenient for cleaning the internal area and fully disinfecting. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The utility model is further described below in conjunction with the accompanying drawings and embodiments.

[0013] Figure 1 It is a schematic diagram of the structure of a single culture area biochip.

[0014] Figure 2 It is a cross-sectional view of a single culture area biochip.

[0015] Figure 3 It is an exploded view of a single culture area biochip.

[0016] Figure 4 It is a schematic diagram of the upper side of the lower plate of the single culture area biochip.

[0017] Figure 5It is a schematic diagram of the bottom side of the lower plate of the single culture area biochip.

[0018] Figure 6 It is a schematic diagram of an adjusting column of the utility model.

[0019] Figure 7 It is a schematic diagram of the disc reed of the utility model.

[0020] Figure 8 It is a schematic diagram of a multi-culture area biochip.

[0021] Fig. 9 This is a diagram of the internal structure of a multi-culture zone biochip.

[0022] Fig.10 It is an exploded view of a multi-culture area biochip.

[0023] Fig.11 It is a schematic diagram of the microcolumn array of the multi-culture area biochip.

[0024] Fig.12 It is a cross-sectional view of a multi-culture zone biochip.

[0025] Fig.13 This is a structural diagram of the partition plates of a multi-culture zone biochip.

[0026] In the figure: upper plate 1; liquid inlet 101; culture chamber 102; liquid outlet 103; bolt hole 104; first sealing gasket 2; first through hole 201; second through hole 202; third through hole 203; porous mold 3; second sealing gasket 4; through waist groove 401; sinking groove 402; lower plate 5; connecting groove 501; top column 502; flow groove 503; third sealing gasket 504; adjustment column 6; strip baffle 601; rotating shaft 602; annular groove 603; disc spring 7; clamping part 701; U-shaped clamping groove 702; cutting groove 703; partition partition 8; strip partition groove 801; label groove 802; magnetic block 803; label sheet 9; culture area 10. DETAILED DESCRIPTION

[0027] Embodiment 1:

[0028] like Figure 1-7 In the present invention, a biochip structure for cell co-culture includes a stacked upper plate 1 and a lower plate 5, the upper plate 1 is provided with a liquid inlet 101 and a liquid outlet 103, at least two culture chambers 102 are provided between the liquid inlet 101 and the liquid outlet 103, the lower plate 5 includes a connecting groove 501, the liquid inlet 101 and the liquid outlet 103 are connected through the connecting groove 501, the lower end of each culture chamber 102 is connected to the connecting groove 501, and a porous membrane 3 is further provided between the upper plate 1 and the lower plate 5, and the porous membrane 3 covers the lower end of each culture chamber 102.

[0029] The liquid inlet 101, the connecting groove 501, and the liquid outlet 103 constitute a U-shaped channel. The culture chamber 102 is located on the line connecting the liquid inlet 101 and the liquid outlet 103 and is located inside the U-shaped structure. Skin or liver tissue can be cultured in different culture chambers 102, and other tissues such as intestines, kidneys, and lungs can also be cultured. The connecting groove 501 simulates blood vessels, and the culture chamber 102 gradually approaches the connecting groove 501 in the depth direction. In other words, the distances between cells at different height layers in the culture chamber 102 and the connecting groove 501 are different, which more realistically simulates the positional relationship between blood vessels and cells.

[0030] The porous membrane 3 is a microporous structure that can block cell penetration. Under the action of the transport pressure, nutrients penetrate from the bottom end to the top end of the culture chamber 102 through the connecting channel 501, and cell metabolic waste can penetrate from the bottom end of 102 to the bottom end into the channel 501, simulating the material exchange between blood and tissues.

[0031] In the preferred embodiment, the first sealing pad 2 and the second sealing pad 4 are respectively provided on the upper and lower sides of the porous membrane 3, the upper plate 1 and the lower plate 5 are closed and clamped with the first sealing pad 2 and the second sealing pad 4 to clamp the porous membrane 3, the first sealing pad 2 is provided with a plurality of second through holes 202, each second through hole 202 is aligned with each culture chamber 102, the second sealing pad 4 is provided with a through waist groove 401, the first sealing pad 2 and the second sealing pad 4 are also provided with a first through hole 201 and a third through hole 203, the first through hole 201 and the third through hole 203 are respectively aligned with the liquid inlet 101 and the liquid outlet 103.

[0032] A plurality of bolt holes 104 aligned in groups are provided on the upper plate 1, the first sealing gasket 2 and the second sealing gasket 4, and the corresponding positions of the bolt holes 104 on the lower plate 5 are threaded holes. Bolts are inserted from the upper plate 1, through the first sealing gasket 2 and the second sealing gasket 4, and the ends are threadedly connected to the lower plate 5, locking the upper plate 1 to the lower plate 5 to improve the sealing effect.

[0033] In a preferred solution, a sinking groove 402 is provided at the through-waist groove 401 , and the porous membrane 3 is placed in the sinking groove 402 .

[0034] The area of ​​the through waist groove 401 is slightly smaller than the porous membrane 3. The sink groove 402 plays a role in positioning the porous membrane 3 to avoid misalignment of the porous membrane 3 during installation. At the same time, it can press the outer edge of the porous membrane 3 to avoid horizontal movement.

[0035] In a preferred solution, a plurality of top columns 502 are provided in the connecting channel 501 , and a flow channel 503 is provided at the upper end of the top column 502 , and the upper end of the top column 502 abuts against the lower end of the porous membrane 3 .

[0036] Since the porous membrane 3 is generally soft, the top pillars 502 at both ends can support the lower end of the second sealing gasket 4 near the outer edge of the porous membrane 3 to press it tightly, and the inner top pillar 502 directly supports the lower end of the porous membrane 3 to prevent the porous membrane 3 from falling and deforming after being filled with cells, gel and other nutrients.

[0037] The flow channel 503 allows the nutrient solution to flow through the contact point between the top of the top column 502 and the porous membrane 3.

[0038] In the preferred embodiment, the top column 502 is provided with multiple rows, and a plurality of rotatable adjusting columns 6 arranged in a straight line are provided in the center of the connecting groove 501. The adjusting column 6 is provided with a strip baffle 601. A rotating shaft 602 is provided at one end of the adjusting column 6. The rotating shaft 602 is rotatably connected to the lower plate 5 and passes through the lower plate 5. An annular groove 603 is provided at the end of the rotating shaft 602, and a plurality of disc spring sheets 7 are also provided. The disc spring sheet 7 is provided with a U-shaped groove 702. A clamping portion 701 is provided at the bottom end of the U-shaped groove 702. The clamping portion 701 is clamped with the annular groove 603, and the outer edge of the disc spring sheet 7 rests against the bottom end of the lower plate 5.

[0039] A plurality of grooves 703 are axially arranged on the outer edge of the disc spring 7 to improve the deformation capability of the disc spring 7 .

[0040] The bottom of the connecting groove 501 is provided with a plurality of threaded holes and light holes. The threaded holes are used to install each top column 502, and the light holes are used to install each adjustment column 6. The third sealing gasket 504 is coated with glue and covers each hole. After the glue solidifies, a small hole is poked at each hole, and the top column 502 and the adjustment column 6 are installed to play a sealing role. The disc spring 7 is elastic. After clamping the adjustment column 6, the adjustment column 6 rotates and presses the third sealing gasket 504, taking into account the sealing.

[0041] Another annular groove can be processed on the rotating shaft 602 and a sealing ring can be sleeved thereon.

[0042] The end of the rotating shaft 602 can be processed with concave and convex stripes to increase muscle friction and facilitate finger rotation.

[0043] By adjusting the regulating column 6 below a certain culture chamber 102 to change the flow area here in the connecting channel 501, the liquid level of the culture solution in the culture chamber 102 can be adjusted. For example, by reducing the flow area, according to the Bernoulli principle, the flow velocity of the connecting channel 501 at the lower end of a certain culture chamber 102 increases, and the pressure here decreases. The pressure is not enough to support the original liquid level, so the liquid level of the culture solution in the upper culture chamber 102 drops. Since the upper plate 1 and the lower plate 5 are made of transparent materials, the liquid level in the culture chamber 102 can be visually observed, and the end of the bottom regulating column 6 can be rotated until the required height is reached. It is also possible to engrave an arrow on the lower end of the regulating column 6 and a scale line on the bottom end of the lower plate 5 to quantitatively adjust the rotation angle of the regulating column 6.

[0044] In a preferred embodiment, the pore size of the porous membrane 3 is 0.4-1 μm.

[0045] Embodiment 2:

[0046] like Figure 6-13 In the invention, an array cell culture chip structure is provided, comprising a stacked upper plate 1 and a lower plate 5, the upper plate 1 comprising a plurality of culture areas 10 arranged side by side, with spacing between adjacent culture areas 10, each culture area 10 comprising a liquid inlet 101 and a liquid outlet 103 arranged at both ends, a plurality of culture chambers 102 are arranged between the liquid inlet 101 and the liquid outlet 103, the liquid inlet 101, the culture chamber 102 and the liquid outlet 103 are arranged in a straight line, the lower plate 5 comprises a plurality of parallel and spaced connecting grooves 501, each connecting groove 501 is located below each culture area 10, the liquid inlet 101 and the liquid outlet 103 are connected through the connecting groove 501, the lower end of each culture chamber 102 is connected to the connecting groove 501, a plurality of porous membranes 3 are further arranged between the upper plate 1 and the lower plate 5, each porous membrane 3 covers the lower end of each culture chamber 102 in the culture area 10.

[0047] Each culture area 10 can work independently and is equipped with a liquid inlet 101 , a liquid outlet 103 , and a plurality of culture chambers 102 .

[0048] In the preferred embodiment, the first sealing pad 2 and the second sealing pad 4 are respectively provided on the upper and lower sides of the porous membrane 3, the upper plate 1 and the first sealing pad 2 are folded and clamped to clamp the first sealing pad 2 and the second sealing pad 4 to clamp the porous membrane 3, the first sealing pad 2 is provided with a plurality of second through holes 202, each second through hole 202 is aligned with each culture chamber 102, the second sealing pad 4 is provided with a through waist groove 401, the first sealing pad 2 and the second sealing pad 4 are also provided with a first through hole 201 and a third through hole 203, the first through hole 201 and the third through hole 203 are respectively aligned with the liquid inlet 101 and the liquid outlet 103.

[0049] In a preferred solution, a sinking groove 402 is provided at the through-waist groove 401 , and the porous membrane 3 is placed in the sinking groove 402 .

[0050] In a preferred embodiment, a plurality of top columns 502 are provided in the connecting channel 501 , and a flow channel 503 is provided at the upper end of the top column 502 , and the upper end of the top column 502 abuts against the lower end of the porous membrane 3 .

[0051] In the preferred embodiment, the top column 502 is provided with multiple rows, and a plurality of rotatable adjusting columns 6 arranged in a straight line are provided in the center of the connecting groove 501. The adjusting column 6 is provided with a strip baffle 601. A rotating shaft 602 is provided at one end of the adjusting column 6. The rotating shaft 602 is rotatably connected to the lower plate 5 and passes through the lower plate 5. An annular groove 603 is provided at the end of the rotating shaft 602, and a plurality of disc spring sheets 7 are also provided. The disc spring sheet 7 is provided with a U-shaped groove 702. A clamping portion 701 is provided at the bottom end of the U-shaped groove 702. The clamping portion 701 is clamped with the annular groove 603, and the outer edge of the disc spring sheet 7 rests against the bottom end of the lower plate 5.

[0052] In the preferred embodiment, a partition partition 8 is further provided at the upper end of the upper plate 1, and the partition partition 8 includes a plurality of parallel and spaced strip partition grooves 801, each of which is arranged above each culture area 10, and a plurality of label grooves 802 are provided on one side of the strip partition groove 801, each of which is provided with a magnetic block 803, and a plurality of label sheets 9 are also provided, the label sheets 9 are arranged in the label grooves 802 and adsorbed by the magnetic blocks 803, and one end of the label sheets 9 points to the culture chamber 102.

[0053] Since there are many culture areas 10 and many culture chambers 102 in the culture areas 10, the residual liquid adhering to the upper surface of the upper plate 1 when adding cells and reagents may flow into the adjacent culture areas 10, causing contamination. Therefore, partition partitions 8 are added and partition grooves 801 are used to separate different culture areas 10, and label sheets 9 are provided to number or add text marks to each culture chamber 102 to avoid confusion.

[0054] Embodiment 3:

[0055] A vascularized skin-liver chip and a method for constructing tissue on a chip thereof, comprising a first layer chip, a second layer chip, a third layer chip, a fourth layer chip and a fifth layer chip stacked in sequence from top to bottom.

[0056] The first layer chip includes a blood inlet, a blood outlet, a skin tissue culture area, a liver tissue culture area, and 6 screw holes. The material is PMMA (laser etching process) or PLA (3D printing process), with a thickness of 6~10mm. All structures run through the first layer chip; the skin tissue culture area, the blood inlet and the blood outlet can be cylindrical, elliptical, rounded rectangular, etc. The size of the skin tissue culture area is 3~15mm, and the size of the blood inlet and outlet is 3~15mm;

[0057] The second layer chip includes a blood inlet through hole, a blood outlet through hole, a skin tissue culture area through hole, a liver tissue culture area through hole, and 6 screw holes. The material is a silicone film used to seal the chip with a thickness of 0.1~1mm. The above structural dimensions and positions correspond one by one to the structural dimensions and positions on the first layer chip, and all structures run through the second layer chip.

[0058] The third chip area covers the skin tissue culture area and the liver tissue culture area, is used to physically separate the blood channel from the skin tissue culture area and the liver tissue culture area, and provides physical support for tissue culture. The material is a PC or PET porous membrane, and the pore size can be 0.4-1 μm;

[0059] The fourth layer chip includes a blood channel through hole and 6 screw hole through holes, and the material is a silicone film used to seal the chip, with a thickness of 0.1-1 mm, and all structures run through the fourth layer chip;

[0060] The fifth-layer chip includes a blood channel and a micro-column array. The overall design of the blood channel is relatively wide, and the connection between the blood channel and the blood inlet through-hole and the blood outlet through-hole is also designed as a wide channel to minimize flow resistance; the blood channel is located on the upper surface of the chip; the micro-column array is located in the blood channel, and the micro-column design does not contain sharp corners to avoid bubbles being trapped when the fluid is running. The length is 0.5~2mm, the width is 0.5~1mm, and the distance between the micro-columns is 0.5~1.5mm. The micro-column array is used to support the third-layer chip on the one hand to prevent collapse, and on the other hand to mix the liquid in the chip; the fifth-layer chip material is PMMA (laser etching processing) or PLA (3D printing processing), the chip thickness is 3~6mm, the channel depth is 2~5mm, and the channel depth is less than the chip thickness; the blood channel area covers the blood inlet, skin tissue culture area, and blood outlet, and the blood channel through-hole corresponds to the size and position of the blood channel one by one.

[0061] The blood inlet, the blood inlet through hole, the blood channel through hole, the blood channel, the blood outlet through hole, and the blood outlet are connected in sequence.

[0062] Fluid flow in the chip can be driven using a rocker arm or a peristaltic pump:

[0063] When the rocker arm is used to drive the chip fluid, the maximum tilt angle is 15°. When the rocker arm is running, the fluid circulates left and right in the blood channel, simulating the blood circulation in the body.

[0064] When a peristaltic pump is used to drive the chip fluid, the pipes at both ends of the peristaltic pump are respectively connected to the blood inlet and the blood outlet to form a blood circulation.

[0065] The vascularized skin-liver tissue-on-a-chip construction method includes the following steps:

[0066] S1. Sterilize the vascularized skin-liver chip and keep it ready for use.

[0067] S2, vascular tissue cell suspension: umbilical vein endothelial cells (5×10 6 / mL) were suspended in type I rat tail collagen or bovine fibrin for later use;

[0068] S3, vascular tissue construction: Use a pipette to add a certain volume of vascular tissue cell suspension directly to the skin tissue culture area and liver tissue culture area from above, and place it in an incubator for 30 minutes to allow the cell-gel mixture to solidify;

[0069] S4, skin tissue cell suspension: keratinocytes (1×10 6 Fibroblasts (1×10 6 / mL) were suspended in type I rat tail collagen or bovine fibrin for later use;

[0070] S5. Skin tissue construction: The fibroblast collagen suspension was directly injected into the skin tissue culture area, with the skin tissue directly above the vascular tissue, and placed in an incubator for 30 minutes to allow the cell-gel mixture to solidify, followed by inoculation of 100 μL of keratinocyte suspension on it and allowing it to stand for 1 hour to allow the cells to attach;

[0071] S6. Slowly add culture medium from the blood inlet until all the gas is discharged from the blood outlet. The amount of culture medium added is 600~1000μL. Place it on the rocker arm or connect it to the peristaltic pump system for dynamic culture. The height of the culture medium at the blood inlet and blood outlet must not exceed the horizontal line of the upper surface of the skin tissue, otherwise it will be detrimental to the formation of the gas-liquid interface.

[0072] S7. Inducing epidermal differentiation: The culture medium in the skin tissue culture area is aspirated, and the culture medium in the blood channel is replaced with an epidermal differentiation culture medium containing calcium ions to construct a skin tissue with an air-liquid interface culture microenvironment. Under this condition, skin tissue with a stratum corneum can be formed after 14 days of culture;

[0073] S8, liver tissue cell suspension: hepatocytes (4×10 6 / mL), hepatic stellate cells (0.2×10 6 / mL) and liver macrophages (0.1×10 6 / mL) were mixed and suspended in type I rat tail collagen or bovine fibrin for later use;

[0074] S9. Liver tissue construction: A certain volume of liver tissue cell suspension is added directly to the liver tissue culture area from above. The liver tissue is directly located above the vascular tissue. It is placed in an incubator and allowed to stand for 30 minutes to allow the cell-gel mixture to solidify. Culture medium is added to the liver tissue culture area. Functionally mature liver tissue can be formed after 4 days of culture.

[0075] The above embodiments are only preferred technical solutions of the present invention and should not be regarded as limitations of the present invention. The protection scope of the present invention shall be the technical solutions recorded in the claims, including equivalent replacement solutions of the technical features in the technical solutions recorded in the claims. That is, equivalent replacement improvements within this scope are also within the protection scope of the present invention.

Claims

1. A biochip structure for cell co-culture, characterized by: The invention comprises a stacked upper plate (1) and a lower plate (5), wherein the upper plate (1) is provided with a liquid inlet (101) and a liquid outlet (103), and at least two culture chambers (102) are provided between the liquid inlet (101) and the liquid outlet (103), and the lower plate (5) comprises a connecting groove (501), wherein the liquid inlet (101) and the liquid outlet (103) are connected via the connecting groove (501), and the lower end of each culture chamber (102) is connected to the connecting groove (501), and a porous membrane (3) is further provided between the upper plate (1) and the lower plate (5), and the porous membrane (3) covers the lower end of each culture chamber (102).

2. The biochip structure for cell co-culture according to claim 1, characterized in that: A first sealing pad (2) and a second sealing pad (4) are respectively provided on the upper and lower sides of the porous membrane (3); the upper plate (1) and the lower plate (5) are closed and clamp the first sealing pad (2) and the second sealing pad (4) to clamp the porous membrane (3); a plurality of second through holes (202) are provided on the first sealing pad (2); each second through hole (202) is aligned with each culture chamber (102); a through waist groove (401) is provided on the second sealing pad (4); a first through hole (201) and a third through hole (203) are also provided on the first sealing pad (2) and the second sealing pad (4); the first through hole (201) and the third through hole (203) are respectively aligned with the liquid inlet (101) and the liquid outlet (103).

3. The biochip structure for cell co-culture according to claim 2, characterized in that: A sinking groove (402) is provided at the through-waist groove (401), and the porous membrane (3) is placed in the sinking groove (402).

4. The biochip structure for cell co-culture according to claim 1, characterized in that: A plurality of top columns (502) are arranged in the connecting channel (501), a flow channel (503) is arranged at the upper end of the top column (502), and the upper end of the top column (502) abuts against the lower end of the porous membrane (3).

5. The biochip structure for cell co-culture according to claim 4, characterized in that: The top column (502) is provided with a plurality of rows, and a plurality of rotatable adjustment columns (6) arranged in a straight line are provided in the center of the connecting groove (501). The adjustment column (6) is provided with a strip-shaped baffle (601). A rotating shaft (602) is provided at one end of the adjustment column (6). The rotating shaft (602) is rotatably connected to the lower plate (5) and passes through the lower plate (5). An annular groove (603) is provided at the end of the rotating shaft (602). A plurality of disc springs (7) are also provided. The disc springs (7) are provided with a U-shaped groove (702). A clamping portion (701) is provided at the bottom end of the U-shaped groove (702). The clamping portion (701) is clamped with the annular groove (603). The outer edge of the disc spring (7) abuts against the bottom end of the lower plate (5).

6. The biochip structure for cell co-culture according to claim 1, characterized in that: The pore size of the porous membrane (3) is 0.4~1 μm.

Images