Bioreactor device for replacing kidney tubule function

Abstract

The utility model provides a bioreactor device for replacing the function of a renal tubule, the bioreactor device is placed in a cell culture incubator, the bioreactor device comprises a fixed frame and a chip, the chip is arranged on the fixed frame, and a vein-imitated renal tubule structure is formed in the chip; openings in the two ends of the flow channel are respectively a liquid inlet and a liquid outlet; the inner diameter of the main flow channel is larger than that of the micro flow channel; wherein the inner diameter of the main flow channel and the inner diameter of the micro flow channel of the chip are both within the pipe diameter range of the physiological renal tubule; a human renal tubular epithelial cell suspension enters the vein-imitating flow channel from the liquid inlet and is attached to the inner wall of the vein-imitating flow channel. Therefore, the structure of the renal tubule is reflected in a more bionic and more reasonable manner, the physiological environment of the renal tubule can be simulated more accurately, a new design thought and method are provided for a renal tubule bioreactor device in a bioartificial kidney, the difficulty in the field of kidney replacement therapy is expected to be solved, and the life quality of patients with end-stage renal failure due to nephropathy is improved.

Description

Technical Field

[0001] The utility model relates to the technical field of kidney replacement, in particular to a bioreactor device for replacing the function of renal tubules. Background Art

[0002] In recent years, the bioartificial kidney (BKI) is a very promising renal function replacement therapy produced through bioengineering technology. It mainly consists of two parts: a blood filter that replaces the glomerular filtration function and a bioreactor that replaces the renal tubular function. It aims to replace most of the kidney's filtration, reabsorption, secretion and metabolic functions. Currently, the principle of blood filtration devices is consistent with that of dialysis machines, and a variety of materials have been used to make blood filtration membranes, such as cellulose membranes, polysulfone membranes, polyethersulfone membranes, and polyamide membranes. However, the core and difficulty of the bioartificial kidney device is that the bioreactor containing living renal tubular epithelial cells is designed to replace the renal tubular reabsorption function.

[0003] Existing bioreactor devices used in bioartificial kidneys typically seed living renal tubular epithelial cells as a monolayer on the inner surface of a hollow fiber membrane or a silicon nanoporous membrane, aiming to replace the renal tubular reabsorption function. Culture medium is dynamically perfused through the top of the cells. Additionally, there are studies using organ-on-a-chip devices to construct renal tubular bioreactors. These devices utilize external dynamic perfusion to ensure nutrient supply to the living cells and maintain cell activity.

[0004] Existing renal tubular bioreactor devices exhibit certain differences from the microstructure of physiological human renal tubules. The renal tubules consist of proximal tubules, thin segments, and distal tubules, all constructed with a cannulated structure. The proximal tubule has an inner diameter of 50-60 μm, the thin segment has an inner diameter of 10-15 μm, and the distal tubule has an inner diameter of 45-300 μm. In most current renal tubular bioreactor devices, renal tubular epithelial cells adhere to the inner tubular wall, and the tubular inner diameter is fixed, including inlet and outlet ports, enabling a preliminary representation of the local microenvironment of the renal tubule. However, these devices fail to fully represent the entire renal tubular structure, resulting in deficiencies in simulating the physiological functions of the renal tubules. Consequently, the construction of renal tubular bioreactors in bioartificial kidney devices still requires rationalization and biomimetic design.

[0005] Therefore, providing a rationally constructed and biomimetic renal tubular bioreactor device is an urgent problem to be solved. Utility Model Content

[0006] The main purpose of the present invention is to provide a bioreactor device for replacing the function of renal tubules, so as to at least solve the problem that the renal tubular bioreactor device in the prior art can only preliminarily present the local microenvironment of the renal tubules, and is therefore insufficient in simulating the physiological function of the renal tubules.

[0007] In order to achieve the above-mentioned object, the utility model provides a bioreactor device for replacing the function of renal tubules, the bioreactor device is placed in a cell culture incubator, and the bioreactor device includes: a fixing frame and a chip;

[0008] The chip is mounted on a fixed frame, and a leaf-vein-like renal tubular structure is formed inside the chip. The leaf-vein-like renal tubular structure includes a main channel with openings at both ends, and multiple microchannels directly and indirectly connected to the main channel. The main channel has a liquid inlet and a liquid outlet at both ends, respectively. The inner diameter of the main channel is larger than that of the microchannel.

[0009] Among them, the inner diameters of the main channel and the microchannel of the chip are both within the diameter range of physiological renal tubules; the human renal tubular epithelial cell suspension enters the leaf-vein-shaped renal tubular structure from the liquid inlet and adheres to the inner wall of the leaf-vein-shaped renal tubular structure.

[0010] Furthermore, the chip is made of polydimethylsiloxane.

[0011] Furthermore, the chip includes a lower chip and an upper cover; a leaf-vein-shaped renal tubular structure is provided on the upper surface of the lower chip; the upper cover fits tightly against the upper surface of the lower chip to completely cover the upper surface of the leaf-vein-shaped renal tubular structure, thereby forming a flow channel in the chip that is open at both ends and closed on all sides.

[0012] Furthermore, the lower chip and the upper cover sheet have the same thickness.

[0013] Furthermore, the fixing frame includes two clamping plates and threaded fasteners; the two clamping plates are respectively arranged on the upper and lower sides of the chip to clamp the chip between the two clamping plates; the threaded fasteners include screws and nuts, and the threaded fasteners are used to fix the two clamping plates;

[0014] Among them, a plurality of fixing holes are correspondingly opened on the two clamping plates, and the plurality of fixing holes are evenly distributed around the outer edge of the chip; the threaded fasteners pass through the corresponding fixing holes above and below the two clamping plates to fix the two clamping plates.

[0015] Furthermore, the bioreactor device further comprises a liquid conveying structure, which comprises a liquid inlet pipe and a liquid outlet pipe; the liquid inlet pipe is connected to the liquid inlet; the liquid outlet pipe is connected to the liquid outlet;

[0016] Among them, the liquid inlet pipe and the liquid outlet pipe are made of Teflon material.

[0017] Furthermore, two conduit holes are respectively provided on the upper and lower sides of the two splints, and the two conduit holes on the two sides are used to allow the liquid inlet pipe and the liquid outlet pipe to pass through respectively;

[0018] The two conduit holes on both sides are respectively located between the fixing hole and the outer edge of the chip, and the liquid inlet pipe and the liquid outlet pipe respectively pass through one of the two corresponding conduit holes above and below.

[0019] Furthermore, the bioreactor device further comprises a micro pump; the micro pump is connected to the leaf vein-shaped renal tubular structure via a liquid inlet tube;

[0020] Among them, the micro pump is used to inject human renal tubular epithelial cell suspension and cell culture medium into the leaf vein-shaped renal tubular structure.

[0021] Furthermore, the bioreactor device also includes a recovery cup, in which the liquid outlet tube is fixed; the recovery cup is used to recover the cell culture fluid that is not adhered to the wall.

[0022] Furthermore, a steel pipe is connected between the liquid inlet pipe and the liquid inlet; and a steel pipe is connected between the liquid outlet pipe and the liquid outlet.

[0023] A bioreactor device for replacing renal tubular function employing the technical solution of the present invention is placed in a cell culture incubator. The bioreactor device comprises a fixing frame and a chip, the chip being arranged on the fixing frame. The chip has a leaf-vein-like renal tubular structure formed inside the chip. The leaf-vein-like renal tubular structure comprises a main channel with openings at both ends, and a plurality of microchannels directly and indirectly connected to the main channel. The main channel has a liquid inlet and a liquid outlet at both ends, respectively. The inner diameter of the main channel is larger than the inner diameter of the microchannel. The inner diameters of the main channel and the microchannel of the chip are both within the diameter range of physiological renal tubules. A suspension of human renal tubular epithelial cells enters the leaf-vein-like channel from the liquid inlet and adheres to the inner wall of the channel. This allows for a more biomimetic and reasonable representation of the renal tubular structure, enabling a more accurate simulation of the physiological environment of the renal tubule. This provides new design ideas and methods for renal tubular bioreactor devices in bioartificial kidneys, and is expected to address the difficulties in the field of renal replacement therapy and improve the quality of life of patients with end-stage renal disease and renal failure. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The drawings constituting part of this application are provided to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are provided to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0025] Figure 1 This is an exploded schematic diagram of a bioreactor device structure for replacing the function of renal tubules according to an embodiment of the present utility model;

[0026] Figure 2 This is a schematic diagram of the structural assembly of a bioreactor device for replacing the function of renal tubules according to an embodiment of the present utility model;

[0027] Figure 3 A schematic diagram of a lower chip structure optional according to an embodiment of the present utility model.

[0028] The above drawings include the following reference numerals:

[0029] 10. Fixing frame; 11. Clamp; 12. Fastener; 121. Screw; 122. Nut; 20. Chip; 21. Lower chip; 22. Upper cover; 30. Leaf-vein-shaped renal tubular structure; 40. Liquid transport structure; 41. Liquid inlet pipe; 42. Liquid outlet pipe. DETAILED DESCRIPTION

[0030] It should be noted that, in the absence of conflict, the embodiments and features of the embodiments in this application can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0031] like Figure 1 、 Figure 2 and Figure 3 As shown, a bioreactor device for replacing the function of renal tubules is placed in a cell culture incubator and includes a fixing frame 10 and a chip 20. The chip 20 is placed on the fixing frame, and a leaf-vein-like renal tubular structure 30 is formed inside the chip 20. The leaf-vein-like renal tubular structure 30 includes a main channel with openings at both ends, and multiple microchannels directly and indirectly connected to the main channel. The openings at both ends of the main channel respectively serve as a liquid inlet and a liquid outlet. The inner diameter of the main channel is larger than the inner diameter of the microchannel.

[0032] The inner diameters of the main channel and the microchannel of the chip 20 are both within the diameter range of physiological renal tubules; the human renal tubular epithelial cell suspension enters the leaf vein-like renal tubular structure 30 from the liquid inlet and adheres to the inner wall of the leaf vein-like renal tubular structure 30.

[0033] Specifically, the bioreactor device is entirely placed in a cell culture incubator. The function of the cell culture incubator is to provide a stable and sterile environment suitable for cell growth, ensuring that the renal tubular epithelial cells can survive normally and perform their reabsorption function. The fixing frame 10 provides a stable support platform for the chip 20, so that the chip 20 can maintain a fixed position and posture in the cell culture incubator. The leaf-vein-like renal tubular structure in the chip includes a complex branching structure similar to leaf veins, which can highly simulate the actual morphology and function of human renal tubules. Human renal tubular epithelial cells are infused into the leaf-vein-like renal tubular structure 30 through the liquid inlet, and adhere to the wall to form a structure similar to the renal tubular lumen. This provides a more realistic and suitable growth environment for human renal tubular epithelial cells. The inner diameters of both the main and microchannels of the chip 20 are within the range of physiological renal tubular diameters. The largest channel, the main channel, has an inner diameter of 150 μm. The smallest inner diameter of the microchannels, directly and indirectly connected to the main channel, is approximately 10 μm. This inner diameter range corresponds to the physiological renal tubular diameters of 50-60 μm for the proximal tubule, 10-15 μm for the slender segment, and 45-300 μm for the distal tubule. This better matches the diameters of different renal tubular regions under physiological conditions, providing a new concept for in vitro simulation of the renal tubular microenvironment.

[0034] Chip 20 is fabricated from polydimethylsiloxane (PDMS) using a photolithographic leaf vein silicon wafer mold. The material of chip 20 in this application should exhibit good biocompatibility with human renal tubular epithelial cells, ensuring that the cells are not affected by the material itself during growth. Furthermore, the surface of chip 20 should facilitate cell attachment and growth, promoting the formation of a structure similar to the renal tubular lumen.

[0035] The bioreactor device in this application more mimics and more rationally reflects the structure of the renal tubules, can further enhance the renal tubular reabsorption function, and can more accurately simulate the physiological environment of the renal tubules. It provides new design ideas and methods for the renal tubular bioreactor device in the bioartificial kidney, which is expected to solve the difficulties in the field of renal replacement therapy and improve the quality of life of patients with end-stage renal disease and renal failure. The human renal tubular epithelial cells in this application are immortalized human renal tubular epithelial cells transformed by lentiviral transfection of primary human renal tubular epithelial cells.

[0036] In a possible implementation, the chip 20 is made of polydimethylsiloxane.

[0037] Specifically, polydimethylsiloxane is abbreviated as PDMS. PDMS has good biocompatibility, elasticity and plasticity, excellent gas permeability and optical transparency, and is simple to manufacture and has low cost.

[0038] In a possible embodiment, the chip 20 also includes a lower chip 21 and an upper cover plate 22, and the upper surface of the lower chip 21 is provided with a leaf-vein-shaped renal tubular structure 30; the upper cover plate 22 fits tightly against the upper surface of the lower chip 21 and completely covers the upper surface of the leaf-vein-shaped renal tubular structure 30, so as to form a flow channel in the chip 20 that is open at both ends and closed on all sides.

[0039] Specifically, the leaf-vein-shaped renal tubular structure opened on the upper surface of the lower chip 21 is tightly fitted with the upper cover 22 to form a flow channel that is open at both ends and closed on all sides, ensuring that the human renal tubular epithelial cell suspension will not leak during the perfusion process and can flow according to the designed leaf-vein-shaped renal tubular structure, thereby providing a stable and controllable growth environment for human renal tubular epithelial cells.

[0040] In a possible implementation manner, the lower chip 21 and the upper cover chip 22 have the same thickness.

[0041] Specifically, the lower chip 21 and the upper cover 22 have the same thickness, which can ensure that the middle leaf vein-like renal tubular structure 30 is evenly stressed, and prevent the microchannels in the leaf vein-like renal tubular structure 30 from being deformed due to uneven pressure.

[0042] In one possible embodiment, the fixing frame 10 includes two clamping plates 11 and a threaded fastener 12; the two clamping plates 11 are respectively disposed on the upper and lower sides of the chip 20 to clamp the chip 20 between the two clamping plates 11; the threaded fastener 12 includes a screw 121 and a nut 122, and the threaded fastener 12 is used to fix the two clamping plates 11;

[0043] The two clamping plates 11 are provided with a plurality of fixing holes, which are evenly distributed around the outer edge of the chip 20 ; the threaded fasteners 12 pass through the corresponding fixing holes on the upper and lower sides of the two clamping plates 11 to fix the two clamping plates 11 .

[0044] Specifically, the threaded fastener 12 includes a screw 121 and a nut 122. The threaded fastener 12 is fixed through the corresponding fixing holes on the upper and lower sides of the two clamps 11, making the installation and disassembly process simple and quick. In addition, the material of the clamp is acrylic, and the two clamps 11 have a plurality of fixing holes evenly distributed around the outer edge of the chip 20. The threaded fastener 12 is fixed through the corresponding fixing holes on the upper and lower sides of the two clamps 11, which can ensure that the pressure generated by the threaded fastener 12 during fixation is evenly distributed around the chip, avoiding deformation or damage to the chip caused by uneven pressure. Moreover, since the fixing holes are evenly distributed around the outer edge of the chip, this design has a certain degree of flexibility and can adapt to chips of different sizes. It is only necessary to adjust the position and number of the threaded fasteners to ensure that the chip is stably clamped and easy to install and disassemble.

[0045] In one possible implementation of prevention and control, the bioreactor device also includes a liquid conveying structure 40, which includes: an inlet pipe 41 and a liquid outlet pipe 42; the inlet pipe 41 is connected to the liquid inlet; the outlet pipe 42 is connected to the liquid outlet; wherein the inlet pipe 41 and the outlet pipe 42 are made of Teflon material.

[0046] Specifically, the input and output of the fluid can be more conveniently controlled through the liquid inlet pipe 41 and the liquid outlet pipe 42. In addition, the Teflon material is resistant to high temperatures and can be used after being sterilized under high pressure.

[0047] In a possible embodiment, two conduit holes are respectively provided on the upper and lower sides of the two splints 11, and the two conduit holes on the two sides are used to allow the liquid inlet pipe 41 and the liquid outlet pipe 42 to pass through respectively;

[0048] The two conduit holes on both sides are respectively located between the fixing hole and the outer edge of the chip 20 , and the liquid inlet pipe 41 and the liquid outlet pipe 42 respectively pass through one of the two corresponding conduit holes.

[0049] Specifically, both splints 11 are provided with catheter holes, through which the liquid inlet and outlet pipes can be conveniently passed and connected to the liquid inlet and outlet of the leaf-vein-shaped renal tubular structure 30, so that the human renal tubular epithelial cell suspension can smoothly enter and leave the chip, ensuring that the fluid management during the cell culture process is more convenient and efficient. In addition, the design of the catheter holes allows the liquid inlet and outlet pipes to be easily disassembled and replaced when needed, thereby improving the maintainability of the entire bioreactor device. The two splints 11 are respectively provided with two catheter holes corresponding to each other on the upper and lower sides. When installing the liquid inlet pipe 41 and the liquid outlet pipe 42, the liquid inlet pipe 41 can pass through any one of the two corresponding catheter holes on the upper and lower sides on the left side, and the liquid outlet pipe 42 can also pass through any one of the two corresponding catheter holes on the upper and lower sides on the right side, which is more convenient to use.

[0050] Liquid flow holes are also provided on the upper cover 22, which correspond to the liquid inlet and liquid outlet of the leaf-vein-like renal tubular structure 30 respectively. The liquid inlet pipe 41 and the liquid outlet pipe 42 pass through the catheter orifice respectively and are inserted into the liquid flow holes on the same side to connect with the liquid inlet and liquid outlet of the leaf-vein-like renal tubular structure 30 respectively.

[0051] In one possible embodiment, the bioreactor device further includes a micro pump; the micro pump is connected to the leaf vein-shaped renal tubular structure 30 via a liquid inlet tube 41;

[0052] The micro pump is used to inject a human renal tubular epithelial cell suspension and a cell culture medium into the leaf-vein-shaped renal tubular structure 30 .

[0053] Specifically, a micropump is used to inject a suspension of human renal tubular epithelial cells into the leaf-vein-like tubular structure 30 from the inlet via the inlet tube 41. After the human renal tubular epithelial cells adhere to the inner wall of the leaf-vein-like tubular structure 30, the micropump is used to deliver cell culture fluid to the inlet of the leaf-vein-like tubular chip. The micropump can deliver cell culture fluid to the inlet of the leaf-vein-like tubular chip at a very precise rate, simulating the flow rate and pressure of physiological fluids in the renal tubules. The flow rate of the micropump can be precisely controlled to 0.4 mm / s. By delivering cell culture fluid from the inlet to the leaf-vein-like tubular structure 30 through the micropump, the flow rate in the main channel can be controlled. The natural channels of the leaf-vein-like tubular structure 30 help control the flow rate in different regions, ensuring that the microchannel diameter matches the flow rate. This can more accurately simulate the flow rate of tubular fluid in the renal tubules in vivo, overcoming the shortcomings of traditional organ chips with single flow channels and flow rates.

[0054] In a possible embodiment, the bioreactor device further includes a recovery cup, in which the liquid outlet tube 42 is fixed; the recovery cup is used to recover the cell culture fluid that is not adhered to the wall.

[0055] Specifically, the recovery cup is used to recover the cell culture fluid that is not attached to the wall, which can save resources and reduce possible pollution to the environment.

[0056] In a possible implementation, a steel pipe is connected between the liquid inlet pipe 41 and the liquid inlet; and a steel pipe is connected between the liquid outlet pipe 42 and the liquid outlet.

[0057] Specifically, the steel tube can effectively enhance the connection stability between the inlet and outlet tubes and the inlet and outlet ports, ensuring the continuity and stability of the human renal tubular epithelial cell suspension during transmission, helping to maintain a stable cell culture environment.

[0058] Further illustrate by the following examples:

[0059] like Figure 1 、 Figure 2 As shown, the bioreactor device includes customized acrylic plate clamps 11 on both sides and an internal chip 20. The four-layer structure is as shown in FIG. Figure 1 As shown, the upper / lower custom acrylic sandwich panels 11 are designed with perforations designed based on the size of the PDMS chip 20. Eight holes with an inner diameter of 0.4 cm are drilled around the PDMS chip 20. Two more holes with an inner diameter of 0.5 cm are drilled inside the holes on the left and right sides. These two holes correspond to the liquid inlet and outlet of the leaf-veined renal tubular structure 30 on the middle PDMS chip 20, respectively. The lower chip 21 and the upper cover sheet 22 are the same size and thickness.

[0060] In the four-layer structure, the upper plywood 11, upper cover sheet 22, lower core 21, and upper plywood 11 are arranged in corresponding order from top to bottom. The upper cover sheet 22 and lower core 21 are bonded together, forming a leaf vein-like flow channel in the middle. The liquid inlet pipe 41 corresponds to the catheter hole on the left side of the upper plywood 11; the liquid outlet pipe 42 corresponds to the catheter hole on the right side of the upper plywood 11. The Teflon-made liquid inlet pipe 41 and liquid outlet pipe 42 pass through the 0.5 cm catheter hole of the upper plywood 11 and the liquid flow hole of the upper cover sheet 22, respectively, and then connect to the liquid inlet and outlet of the leaf vein-like renal tubular structure 30 between the lower core 21 and the upper cover sheet 22. The upper and lower plywood 11 are fixed and locked with screws and nuts through eight 0.4 cm inner diameter holes, tightly fitting the lower core 21 and upper cover sheet 22.

[0061] The liquid inlet tube 41 is connected to a micro pump to pump the human renal tubular epithelial cell suspension into the leaf vein-like renal tubular structure 30. The device is placed in a cell culture incubator overnight to allow a monolayer of human renal tubular epithelial cells to adhere to the inner wall of the leaf vein-like renal tubular structure 30. The liquid outlet tube 42 is connected to a fixed recovery glass beaker to recover the cell culture fluid.

[0062] Figure 3 The schematic diagram of the structure of the lower chip 21 in the core device is shown. After obtaining the network structure of the osmanthus leaf veins through high-quality photography and digitization of decellularized osmanthus leaves, the lower chip 21 with leaf vein microfluidic channels was fabricated using photolithography and soft lithography techniques.

[0063] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that the present invention is susceptible to various modifications and variations. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A bioreactor device for replacing the function of renal tubules, the bioreactor device being placed in a cell culture incubator, characterized in that: The bioreactor device comprises: Fixed frame (10); A chip (20) is provided on the fixing frame, wherein a leaf-vein-like renal tubular structure (30) is formed inside the chip (20), wherein the leaf-vein-like renal tubular structure (30) comprises a main channel with openings at both ends, and a plurality of microchannels directly and indirectly connected to the main channel; the openings at both ends of the main channel are respectively a liquid inlet and a liquid outlet; and the inner diameter of the main channel is larger than the inner diameter of the microchannel; The inner diameters of the main channel and the microchannel of the chip (20) are both within the diameter range of physiological renal tubules; the human renal tubular epithelial cell suspension enters the leaf vein-like renal tubular structure (30) from the liquid inlet and adheres to the inner wall of the leaf vein-like renal tubular structure (30).

2. A bioreactor device for replacing renal tubular function according to claim 1, characterized in that: The chip (20) is made of polydimethylsiloxane.

3. A bioreactor device for replacing renal tubular function according to claim 1, characterized in that: The chip (20) comprises: A lower chip (21), wherein the upper surface of the lower chip (21) is provided with the leaf vein-shaped renal tubular structure (30); An upper cover sheet (22) is tightly fitted to the upper surface of the lower chip (21) to completely cover the upper surface of the leaf vein-shaped renal tubular structure (30), so as to form a flow channel with two ends open and four sides closed in the chip (20).

4. A bioreactor device for replacing renal tubular function according to claim 3, characterized in that: The lower chip (21) and the upper cover (22) have the same thickness.

5. The bioreactor device for replacing renal tubular function according to claim 3, characterized in that: The fixing frame (10) comprises: Two clamping plates (11), the two clamping plates (11) being respectively arranged on the upper and lower sides of the chip (20) to clamp the chip (20) between the two clamping plates (11); A threaded fastener (12), the threaded fastener (12) comprising a screw (121) and a nut (122), the threaded fastener (12) being used to fix the two clamping plates (11); Wherein, a plurality of fixing holes are correspondingly opened on the two clamps (11), and the plurality of fixing holes are evenly distributed around the outer edge of the chip (20); the threaded fastener (12) passes through the corresponding fixing holes above and below the two clamps (11) to fix the two clamps (11).

6. A bioreactor device for replacing renal tubular function according to claim 5, characterized in that: The bioreactor device further comprises a liquid delivery structure (40), wherein the liquid delivery structure (40) comprises: a liquid inlet pipe (41), connected to the liquid inlet; a liquid outlet pipe (42), connected to the liquid outlet; Wherein, the liquid inlet pipe (41) and the liquid outlet pipe (42) are made of Teflon material.

7. A bioreactor device for replacing renal tubular function according to claim 6, characterized in that: Two conduit holes are respectively provided on the upper and lower sides of the two clamping plates (11), and the two conduit holes on the two sides are used to allow the liquid inlet pipe (41) and the liquid outlet pipe (42) to pass through respectively; The two conduit holes on both sides are respectively located between the fixing hole and the outer edge of the chip (20), and the liquid inlet pipe (41) and the liquid outlet pipe (42) respectively pass through one of the two corresponding conduit holes.

8. The bioreactor device for replacing renal tubular function according to claim 6, characterized in that: The bioreactor device further comprises a micro pump; the micro pump is connected to the leaf vein-like renal tubular structure (30) via the liquid inlet tube (41); The micro pump is used to inject a human renal tubular epithelial cell suspension and a cell culture medium into the leaf vein-like renal tubular structure (30).

9. The bioreactor device for replacing renal tubular function according to claim 6, characterized in that: The bioreactor device further comprises a recovery cup, in which the liquid outlet tube (42) is fixed; the recovery cup is used to recover cell culture fluid that is not adhered to the wall.

10. The bioreactor device for replacing renal tubular function according to claim 6, characterized in that: A steel pipe is connected between the liquid inlet pipe (41) and the liquid inlet; and a steel pipe is connected between the liquid outlet pipe (42) and the liquid outlet.

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