Bioartificial liver reactor and bioartificial liver system

By designing evenly arranged flow homogenization poles and flow homogenizers in the biological artificial liver reactor, a stable flow field is formed, which solves the problems of low cell survival rate and low metabolic material transportation efficiency, and achieves more uniform cell culture and efficient metabolic material transportation.

CN120059939APending Publication Date: 2025-05-30CHANGPING NAT LAB
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Patent Information

Application Number
CN202311599465.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2023-11-28
Publication Date
2025-05-30

AI Technical Summary

Technical Problem

The existing biological artificial liver reactors face problems such as cell agglomeration and deposition, uneven delivery of nutrients during the treatment cycle, resulting in low cell survival rate and low efficiency of metabolic material transportation.

Method used

A biological artificial liver reactor is designed, including a container, a first flow coupon and a second flow coupon. A plurality of uniform flow coupons are provided on the flow coupon. Through these flow coupons, a uniform flow of liquid is achieved, a pressure at the inlet is reduced, and a uniform and stable flow field is formed between the first flow coupon and the second flow coupon.

Benefits of technology

This design effectively avoids the problems of cell aggregation and sedimentation, uneven dispersion and uneven delivery of nutrients, improves the survival rate of cells during the treatment cycle, and achieves efficient transportation of metabolic substances.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention relates to a bioartificial liver reactor and a bioartificial liver system.The bioartificial liver reactor comprises a container (1), a first flow equalizing part (2) and a second flow equalizing part (3), the container (1) is provided with a first containing cavity (11), the first end of the container (1) is provided with an inlet (12) communicated with the first containing cavity (11), and the second end of the container (1) is provided with an outlet (13) communicated with the first containing cavity (11); the first flow equalizing part (2) is arranged in the first containing cavity (11) and is close to the inlet (12), a plurality of first flow equalizing holes (21) which are evenly distributed are formed in the first flow equalizing part (2), the second flow equalizing part (3) is arranged in the first containing cavity (11) and is close to the outlet (13), and a plurality of second flow equalizing holes (31) which are evenly distributed are formed in the second flow equalizing part (3). The bioartificial liver system comprises a bioartificial liver reactor.
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Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and particularly to a bioartificial liver reactor and a bioartificial liver system. Background Art

[0002] The liver has functions such as synthesis, detoxification, metabolism, secretion, biotransformation, and immune defense. When severely damaged by viruses or drugs, it can lead to liver failure, and massive necrosis of liver cells causes serious disorders or decompensation of the above functions.

[0003] Currently, artificial liver systems have been widely used in the treatment of liver failure, including non-biological artificial livers, biological artificial livers, and hybrid artificial livers. The principle is to remove harmful substances in the body through an extracorporeal device, supplement essential substances for the human body, improve the internal environment, temporarily replace some functions of the liver, create conditions for surgical treatment, or extend the waiting time for liver transplantation.

[0004] The biological artificial liver system is mainly based on an in vitro bioreactor perfused with liver cells, which exchanges substances with the patient's plasma through a semi-permeable membrane to achieve biotransformation and synthetic liver functions. Among them, the short-term culture of liver cells in the bioreactor still faces problems such as cell aggregation and deposition, and uneven delivery of nutrients. Therefore, there is an urgent need to study a new type of bioartificial liver reactor that can ensure the survival of cells and the efficient transport of metabolites during the treatment cycle.

[0005] It should be noted that the information disclosed in the background art part of the present invention is only intended to increase the understanding of the overall background of the present invention, and should not be regarded as an admission or any form of suggestion that this information constitutes the prior art known to those skilled in the art. The above statements are only used to provide background technical information related to the present application, and do not necessarily constitute the prior art. Summary of the Invention

[0006] Embodiments of the present invention provide a bioartificial liver reactor and a bioartificial liver system, which can provide a uniform and stable reaction space for liver cells.

[0007] According to one aspect of the present invention, there is provided a bioartificial liver reactor, comprising:

[0008] A container having a first accommodation cavity, with an inlet communicating with the first accommodation cavity provided at a first end of the container, and an outlet communicating with the first accommodation cavity provided at a second end of the container;

[0009] A first flow equalizing member disposed inside the first accommodation cavity and adjacent to the inlet, and the first flow equalizing member is provided with a plurality of uniformly arranged first flow equalizing holes; and

[0010] A second flow equalizing member is disposed inside the first accommodating cavity and adjacent to the outlet, and a plurality of uniformly arranged second flow equalizing holes are provided on the second flow equalizing member.

[0011] In some embodiments, the first flow equalizing member includes a first plate body and a support ring disposed on a side of the first plate body close to the inlet. The first flow equalizing holes are provided on the first plate body. The support ring abuts against the inner wall of the first accommodating cavity provided with the inlet. A second accommodating cavity is formed by enclosing the first flow equalizing member and the inner wall of the first accommodating cavity provided with the inlet.

[0012] In some embodiments, the bioartificial liver reactor further includes a first delivery pipe connected to the inlet, and the height of the second accommodating cavity is greater than the length of the first delivery pipe extending into the second accommodating cavity.

[0013] In some embodiments, the plurality of first flow equalizing holes are arranged in a plurality of circles along the radial direction, and the diameter of the first flow equalizing holes located in the outer circle is greater than the diameter of the first flow equalizing holes located in the inner circle; and / or, the plurality of second flow equalizing holes are arranged in a plurality of circles along the radial direction, and the diameter of the second flow equalizing holes located in the outer circle is greater than the diameter of the second flow equalizing holes located in the inner circle.

[0014] In some embodiments, the outer wall of the first flow equalizing member is in close contact with the inner wall of the first accommodating cavity to prevent the first flow equalizing member from moving relative to the first accommodating cavity.

[0015] In some embodiments, the container includes a container body and a cover body. The cover body is detachably mounted on the container body. The internal space of the container body and the internal space of the cover body together form the first accommodating cavity.

[0016] In some embodiments, the outer periphery of the container body is provided with a first external thread, and the inner wall of the cover body is provided with a first internal thread. The container body and the cover body are connected through the cooperation of the first external thread and the first internal thread.

[0017] In some embodiments, the inner wall of the first accommodating cavity provided with the outlet is provided with a boss protruding into the interior of the first accommodating cavity, and a third accommodating cavity is provided inside the boss. The second flow equalizing member is disposed in the third accommodating cavity.

[0018] In some embodiments, the inner wall of the third accommodating cavity is provided with a second internal thread, and the outer periphery of the second flow equalizing member is provided with a second external thread. The second flow equalizing member is mounted on the boss through the cooperation of the second external thread and the second internal thread.

[0019] In some embodiments, there is a gap between the boss and the inner wall of the cover body, and the top of the container body is inserted into the gap.

[0020] In some embodiments, the bioartificial liver reactor further includes a sealing ring disposed between the boss and the inner wall of the cover body.

[0021] In some embodiments, the bioartificial liver reactor further includes a first filter screen disposed on a side of the first flow equalizing member away from the inlet, and the first filter screen is configured to block cells located in the first accommodation cavity from flowing out reversely through the inlet.

[0022] In some embodiments, the bioartificial liver reactor further includes a first fixing member. A first groove is provided on a side of the first flow equalizing member away from the inlet, and the first fixing member is inserted into the first groove to press the edge of the first filter screen into the first groove.

[0023] In some embodiments, the first groove is annular, the first fixing member is annular, and the first fixing member includes a first insertion portion and a first pressing portion arranged along its axial direction. The outer diameter of the first insertion portion is smaller than the outer diameter of the first pressing portion. The first insertion portion is inserted into the first groove, and the first pressing portion presses against the first flow equalizing member.

[0024] In some embodiments, the bioartificial liver reactor further includes a second filter screen disposed on a side of the second flow equalizing member close to the outlet, and the second filter screen is configured to block cells located in the first accommodation cavity from flowing out through the outlet.

[0025] In some embodiments, the bioartificial liver reactor further includes a second fixing member. A second groove is provided on a side of the second flow equalizing member close to the outlet, and the second fixing member is inserted into the second groove to press the edge of the second filter screen into the second groove.

[0026] In some embodiments, the second groove is annular, the second fixing member is annular, and the second fixing member includes a second insertion portion and a second pressing portion arranged along its axial direction. The outer diameter of the second insertion portion is smaller than the outer diameter of the second pressing portion. The second insertion portion is inserted into the second groove, and the second pressing portion presses against the second flow equalizing member.

[0027] According to another aspect of the present invention, there is provided a bioartificial liver system including the above-mentioned bioartificial liver reactor.

[0028] Based on the above technical solutions, the reactor embodiments provided by the present invention include a first flow equalizing member disposed adjacent to the inlet of the container and a second flow equalizing member disposed adjacent to the outlet, which can evenly distribute the liquid entering the container through the inlet through the first flow equalizing member, and evenly distribute the liquid in the container through the second flow equalizing member and then flow out through the outlet, thereby effectively reducing the pressure at the inlet and forming a uniform and stable flow field between the first flow equalizing member and the second flow equalizing member, providing a uniform and stable reaction space for the liver cells in the container, avoiding problems such as cell aggregation and sedimentation, uneven dispersion, and uneven delivery of nutrients, effectively improving the survival rate of cells during the treatment cycle, and realizing the efficient transport of metabolic substances. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The accompanying drawings described herein are used to provide a further understanding of the present invention and form a part of this application. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0030] Figure 1 is a schematic structural diagram of some embodiments of the bioartificial liver reactor provided by the present invention.

[0031] Figure 2 is a schematic structural diagram of the first flow equalizing member in some embodiments of the bioartificial liver reactor provided by the present invention.

[0032] Figure 3 is a schematic structural diagram of the second flow equalizing member in some embodiments of the bioartificial liver reactor provided by the present invention.

[0033] Figure 4 is a schematic structural diagram of the first structure of the cover body in some embodiments of the bioartificial liver reactor provided by the present invention.

[0034] Figure 5 is a schematic structural diagram of the second structure of the cover body in some embodiments of the bioartificial liver reactor provided by the present invention.

[0035] Figure 6 is a schematic structural diagram of the first fixing member in some embodiments of the bioartificial liver reactor provided by the present invention.

[0036] In the figure:

[0037] 1. Container; 11. First accommodation cavity; 12. Inlet; 13. Outlet; 14. Container body; 141. First external thread; 15. Cover body; 151. First internal thread; 152. Boss; 153. Second internal thread; 2. First flow equalizing member; 21. First flow equalizing hole; 22. First plate body; 23. Support ring; 24. First groove; 3. Second flow equalizing member; 31. Second flow equalizing hole; 32. Second external thread; 33. Second groove; 4. First filter screen; 5. Second filter screen; 6. First fixing member; 61. First insertion part; 62. First pressing part; 7. Second fixing member; 8. First conveying pipe; 9. Second conveying pipe. Detailed implementation manners

[0038] Next, the technical solutions in the embodiments will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0039] In the description of the present invention, it should be understood that the orientation or positional relationship indicated by the terms "center", "lateral", "longitudinal", "front", "rear", "left", "right", "upper", "lower", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings. It 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. Therefore, it should not be construed as a limitation on the protection scope of the present invention.

[0040] Referring Figures 1 to 3 As shown, in some embodiments of the bioartificial liver reactor provided by the present invention, the reactor includes a container 1, a first flow equalizing member 2, and a second flow equalizing member 3. The container 1 is provided with a first accommodating cavity 11. An inlet 12 communicating with the first accommodating cavity 11 is provided at the first end of the container 1, and an outlet 13 communicating with the first accommodating cavity 11 is provided at the second end of the container 1. The first flow equalizing member 2 is disposed inside the first accommodating cavity 11 and adjacent to the inlet 12. A plurality of uniformly arranged first flow equalizing holes 21 are provided on the first flow equalizing member 2. The second flow equalizing member 3 is disposed inside the first accommodating cavity 11 and adjacent to the outlet 13. A plurality of uniformly arranged second flow equalizing holes 31 are provided on the second flow equalizing member 3.

[0041] In the embodiments provided by the present invention, the reactor includes a first flow equalizing member 2 disposed adjacent to the inlet 12 of the container 1 and a second flow equalizing member 3 disposed adjacent to the outlet 13, which can evenly distribute the liquid entering the container 1 through the inlet 12 through the first flow equalizing member 2, and evenly distribute the liquid in the container 1 through the second flow equalizing member 3 and then flow out through the outlet 13, thereby effectively reducing the pressure at the inlet and forming a uniform and stable flow field between the first flow equalizing member 2 and the second flow equalizing member 3, providing a uniform and stable reaction space for the liver cells in the container, avoiding problems such as cell aggregation and sedimentation, uneven dispersion, and uneven delivery of nutrients, effectively improving the survival rate of cells during the treatment cycle, and realizing the efficient transport of metabolic substances.

[0042] In some embodiments, the first flow equalizing member 2 includes a first plate body 22 and a support ring 23 disposed on one side of the first plate body 22 close to the inlet 12. The first flow equalizing holes 21 are provided on the first plate body 22. The support ring 23 abuts against the inner wall of the first accommodating cavity 11 provided with the inlet 12. The first flow equalizing member 2 and the inner wall of the first accommodating cavity 11 provided with the inlet 12 enclose a second accommodating cavity.

[0043] By providing a support ring 23 and abutting the support ring 23 against the inner wall of the first accommodation chamber 11 where the inlet 12 is provided, a certain distance can be formed between the inner wall of the first accommodation chamber 11 where the inlet 12 is provided and the first plate body 22, and a second accommodation chamber is formed therebetween, which can provide a certain buffer space for the liquid entering the container 1 through the inlet 12 and also provide a buffer space for the subsequent flow splitting; it can also prevent the components provided at the inlet 12 from interfering with the first flow equalizing member 2 and affecting the entry of the liquid.

[0044] The support ring 23 is annular and extends from the side of the first plate body 22 close to the inlet 12 towards the inlet 12.

[0045] The support ring 23 and the first plate body 22 can be separately manufactured and connected together; alternatively, the support ring 23 and the first plate body 22 are integrally formed.

[0046] In some embodiments, the support ring 23 can also be replaced by a plurality of support blocks arranged at intervals in the circumferential direction.

[0047] In some embodiments, the bioartificial liver reactor further includes a first delivery pipe 8 connected to the inlet 12, and the height of the second accommodation chamber is greater than the length of the first delivery pipe 8 extending into the second accommodation chamber.

[0048] By setting the height of the second accommodation chamber to be greater than the length of the first delivery pipe 8 extending into the second accommodation chamber, it can prevent the first plate body 22 from blocking the outlet of the first delivery pipe 8 and prevent the first plate body 22 from affecting the entry of the liquid.

[0049] As Figure 2 shown, in some embodiments, a plurality of first flow equalizing holes 21 are arranged in a plurality of circles in the radial direction, and the diameter of the first flow equalizing holes 21 in the outer circle is greater than the diameter of the first flow equalizing holes 21 in the inner circle.

[0050] By setting the diameter of the first flow equalizing holes 21 in the outer circle to be greater than the diameter of the first flow equalizing holes 21 in the inner circle, the flow pressure of the first flow equalizing holes 21 in the outer circle can be reduced, so that the liquid can be more easily dispersed to the outer circle and prevent the liquid from flowing out directly through the first flow equalizing holes 21 in the inner circle, affecting the effect of uniform flow splitting.

[0051] In some embodiments, the distance between two adjacent first flow equalizing holes 21 in the outer circle is greater than the distance between two adjacent first flow equalizing holes 21 in the inner circle.

[0052] By setting the distance between two adjacent first flow equalizing holes 21 in the outer ring to be greater than the distance between two adjacent first flow equalizing holes 21 in the inner ring, the flow pressure in the outer ring can also be reduced, so that the liquid can be more easily dispersed into the outer ring, improving the effect of uniform flow distribution.

[0053] In the embodiments of the present invention, the shape of the first flow equalizing hole 21 can be circular, square or other shapes.

[0054] As Figure 3 shown, in some embodiments, a plurality of second flow equalizing holes 31 are arranged in a plurality of circles along the radial direction, and the diameter of the second flow equalizing holes 31 in the outer ring is greater than the diameter of the second flow equalizing holes 31 in the inner ring.

[0055] By setting the diameter of the second flow equalizing holes 31 in the outer ring to be greater than the diameter of the second flow equalizing holes 31 in the inner ring, the flow pressure of the second flow equalizing holes 31 in the outer ring can be reduced, so that the liquid can be more easily dispersed into the outer ring, avoiding the liquid flowing out directly through the second flow equalizing holes 31 in the inner ring and affecting the effect of uniform flow distribution.

[0056] In some embodiments, the distance between two adjacent second flow equalizing holes 31 in the outer ring is greater than the distance between two adjacent second flow equalizing holes 31 in the inner ring.

[0057] By setting the distance between two adjacent second flow equalizing holes 31 in the outer ring to be greater than the distance between two adjacent second flow equalizing holes 31 in the inner ring, the flow pressure in the outer ring can also be reduced, so that the liquid can be more easily dispersed into the outer ring, improving the effect of uniform flow distribution.

[0058] In the embodiments of the present invention, the shape of the second flow equalizing hole 31 can be circular, square or other shapes.

[0059] In some embodiments, the outer wall of the first flow equalizing member 2 is in close contact with the inner wall of the first accommodation cavity 11 to prevent the first flow equalizing member 2 from moving relative to the first accommodation cavity 11.

[0060] By setting the outer wall of the first flow equalizing member 2 to be in close contact with the inner wall of the first accommodation cavity 11, the first flow equalizing member 2 can be prevented from moving relative to the first accommodation cavity 11 under the impact of the inlet air flow, resulting in unstable flow equalizing effect.

[0061] In some embodiments, an interference fit is provided between the first flow equalizing member 2 and the first accommodation cavity 11 to achieve close contact between the outer wall of the first flow equalizing member 2 and the inner wall of the first accommodation cavity 11.

[0062] In some embodiments, the container 1 includes a container body 14 and a lid 15. The lid 15 is detachably mounted on the container body 14. The internal spaces of the container body 14 and the lid 15 together form a first accommodation cavity 11.

[0063] By setting the container body 14 and the lid 15 to be detachably connected, the lid 15 can be closed during the transportation of the container 1 to maintain the sterility inside the container body 14. When liver cells need to be added into the container body 14, the lid 15 can be opened, and then the liver cells can be added and the lid 15 can be closed again to seal the container body 14.

[0064] In some embodiments, a first external thread 141 is provided on the outer periphery of the container body 14, and a first internal thread 151 is provided on the inner wall of the lid 15. The container body 14 and the lid 15 are connected through the cooperation of the first external thread 141 and the first internal thread 151.

[0065] Adopting a threaded connection between the container body 14 and the lid 15 can achieve a detachable connection between the container body 14 and the lid 15. Moreover, the manufacturing is simple, the cost is low, and the connection reliability is relatively high.

[0066] As Figure 4 and Figure 5 shown, in some embodiments, on the inner wall of the first accommodation cavity 11 where the outlet 13 is provided, a boss 152 protruding towards the inside of the first accommodation cavity 11 is provided, and a third accommodation cavity is provided inside the boss 152. The second flow equalizing member 3 is disposed in the third accommodation cavity. The outlet 13 communicates with the third accommodation cavity.

[0067] By providing the boss 152, it can provide support for the second flow equalizing member 3 and also facilitate the installation of the second flow equalizing member 3. By setting the boss 152 as a hollow structure to form the third accommodation cavity, it can provide an accommodation space for the second flow equalizing member 3, which is beneficial to improving the stability of the second flow equalizing member 3.

[0068] In some embodiments, a second internal thread 153 is provided on the inner wall of the third accommodation cavity, and a second external thread 32 is provided on the outer periphery of the second flow equalizing member 3. The second flow equalizing member 3 is installed on the boss 152 through the cooperation of the second external thread 32 and the second internal thread 153.

[0069] The second flow equalizing member 3 is installed on the boss 152 through a threaded connection, which can improve the convenience of operation and also achieve a detachable connection of the second flow equalizing member 3 to meet the requirement of separately disassembling the second flow equalizing member 3 for disinfection.

[0070] In some embodiments, there is a gap between the boss 152 and the inner wall of the lid 15, and the top of the container body 14 is inserted into the gap.

[0071] By providing a gap between the boss 152 and the inner wall of the cover 15, the top of the container body 14 can be inserted into the gap, enabling the container body 14 to overlap with the boss 152 in the axial direction. Thus, the container body 14 can be positioned by the boss 152 and the inner wall of the cover 15, enhancing the relative stability between the container body 14 and the cover 15.

[0072] In some embodiments, the bioartificial liver reactor further includes a sealing ring disposed between the boss 152 and the inner wall of the cover 15.

[0073] By providing the sealing ring, the threaded connection between the container body 14 and the cover 15 can be sealed, preventing liquid leakage.

[0074] In some embodiments, the bioartificial liver reactor further includes a first filter screen 4 disposed on the side of the first flow equalizing member 2 away from the inlet 12. The first filter screen 4 is configured to prevent cells located in the first accommodation chamber 11 from flowing out reversely through the inlet 12.

[0075] By providing the first filter screen 4 on the side of the first flow equalizing member 2 away from the inlet 12, cells located in the first accommodation chamber 11 can be prevented from flowing out reversely through the inlet 12, avoiding cell loss and affecting the reaction effect.

[0076] In some embodiments, the bioartificial liver reactor further includes a first fixing member 6. A first groove 24 is provided on the side of the first flow equalizing member 2 away from the inlet 12, and the first fixing member 6 is inserted into the first groove 24 to press the edge of the first filter screen 4 into the first groove 24.

[0077] By providing the first fixing member 6 to press the edge of the first filter screen 4 into the first groove 24, relative fixation between the first filter screen 4 and the first flow equalizing member 2 can be achieved.

[0078] Adopting the fixing method of using the first fixing member 6 to press the edge of the first filter screen 4 into the first groove 24 of the first flow equalizing member 2 is convenient for operation, does not damage the first filter screen 4, and can also tighten the surface of the first filter screen 4 during the pressing process to prevent the first filter screen 4 from stacking and affecting the entry of liquid.

[0079] As Figure 6 shown, in some embodiments, the first groove 24 is annular, the first fixing member 6 is annular, and the first fixing member 6 includes a first insertion portion 61 and a first pressing portion 62 arranged along its axial direction. The outer diameter of the first insertion portion 61 is smaller than that of the first pressing portion 62. The first insertion portion 61 is inserted into the first groove 24, and the first pressing portion 62 presses against the first flow equalizing member 2.

[0080] By providing the first insertion portion 61 and the first pressing portion 62, the edge of the first filter screen 4 can be pressed into the first groove 24 of the first flow equalizing member 2 through the first insertion portion 61, while the first pressing portion 62 can press against the first flow equalizing member 2 to play a role in fixing and limiting.

[0081] An interference fit can be adopted between the first insertion portion 61 and the first groove 24 to improve the connection reliability between the first insertion portion 61 and the first groove 24 and prevent the first insertion portion 61 from coming out of the first groove 24.

[0082] In some embodiments, the bioartificial liver reactor further includes a second filter screen 5 disposed on one side of the second flow equalizing member 3 close to the outlet 13, and the second filter screen 5 is configured to block the cells located in the first accommodation cavity 11 from flowing out through the outlet 13.

[0083] By providing the second filter screen 5 on one side of the second flow equalizing member 3 close to the outlet 13, it is possible to prevent the cells located in the first accommodation cavity 11 from flowing out through the outlet 13 and affecting the composition of the output liquid.

[0084] In some embodiments, the bioartificial liver reactor further includes a second fixing member 7. A second groove 33 is provided on one side of the second flow equalizing member 3 close to the outlet 13, and the second fixing member 7 is inserted into the second groove 33 to press the edge of the second filter screen 5 into the second groove 33.

[0085] By providing the second fixing member 7 and pressing the edge of the second filter screen 5 into the second groove 33, relative fixation between the second filter screen 5 and the second flow equalizing member 3 can be achieved.

[0086] Adopting the fixing method of pressing the edge of the second filter screen 5 into the second groove 33 of the second flow equalizing member 3 by the second fixing member 7 is convenient for operation, does not damage the second filter screen 5, and can also tighten the surface of the second filter screen 5 during the pressing process to prevent the second filter screen 5 from stacking and affecting the entry of liquid.

[0087] In some embodiments, the second groove 33 is annular, the second fixing member 7 is annular, and the second fixing member 7 includes a second insertion portion and a second pressing portion arranged along its axial direction. The outer diameter of the second insertion portion is smaller than the outer diameter of the second pressing portion. The second insertion portion is inserted into the second groove 33, and the second pressing portion presses against the second flow equalizing member 3.

[0088] By providing the second insertion portion and the second pressing portion, the edge of the second filter screen 5 can be pressed into the second groove 33 of the second flow equalizing member 3 through the second insertion portion, while the second pressing portion can press against the second flow equalizing member 3 to play a role in fixing and limiting.

[0089] An interference fit can be adopted between the second insertion part and the second groove 33 to improve the connection reliability between the second insertion part and the second groove 33 and prevent the second insertion part from disengaging from the second groove 33.

[0090] In the embodiment provided by the present invention, a plurality of first filter holes are provided on the first filter screen 4, and a plurality of second filter holes are provided on the second filter screen 5. The diameter of the first filter holes is smaller than the diameter of the first flow equalizing holes 21 on the first flow equalizing member 2, and the diameter of the second filter holes is smaller than the diameter of the second flow equalizing holes 31 on the second flow equalizing member 3.

[0091] In some embodiments, the diameter of the first flow equalizing holes 21 and / or the second flow equalizing holes 31 is 1 mm to 2 mm. The diameter of the first filter holes and / or the second filter holes is approximately 5 μm.

[0092] The following Figures 1 to 6 will describe the structure of an embodiment of the bioartificial liver reactor of the present invention with reference to the attached

[0093] As Figure 1 shown, the bioartificial liver reactor includes a container 1, a first flow equalizing member 2, a second flow equalizing member 3, a first filter screen 4, a second filter screen 5, a first fixing member 6, a second fixing member 7, a first delivery pipe 8 and a second delivery pipe 9.

[0094] A first accommodation cavity 11 is provided inside the container 1. An inlet 12 is provided on the bottom surface of the container 1, and an outlet 13 is provided on the top surface of the container 1. The container 1 includes a container body 14 and a cover body 15. Both the container body 14 and the cover body 15 have a certain accommodation space, and the accommodation spaces of the container body 14 and the cover body 15 together form the first accommodation cavity 11. The inlet 12 is provided on the bottom surface of the container body 14, and the outlet 13 is provided on the top surface of the cover body 15.

[0095] A first external thread 141 is provided on the outer periphery of the container body 14, and the first external thread 141 is at a preset distance from the top end surface of the container body 14. A first internal thread 151 is provided on the inner wall of the cover body 15, and the container body 14 and the cover body 15 are connected by the first external thread 141 and the first internal thread 151. Both the container body 14 and the cover body 15 are in the shape of a cylinder.

[0096] The first flow equalizing member 2 is installed inside the first accommodation cavity 11 and close to the inlet 12, and the bottom of the first flow equalizing member 2 abuts against the bottom wall of the first accommodation cavity 11. The first filter screen 4 is located above the first flow equalizing member 2, and the first fixing member 6 is used to connect the first filter screen 4 and the first flow equalizing member 2.

[0097] The second flow equalizing member 3 is installed inside the first accommodation cavity 11 and close to the outlet 13. The second filter screen 5 is located above the second flow equalizing member 3, and the second fixing member 7 is used to connect the second filter screen 5 and the second flow equalizing member 3.

[0098] The first delivery pipe 8 is connected to the inlet 12 and is used to deliver liquid, such as cell culture medium and other substances, into the first accommodation chamber 11. The second delivery pipe 9 is connected to the outlet 13 and is used to discharge the reacted liquid.

[0099] As Figure 2 shown, the first flow equalizing member 2 is in the shape of a cylinder. The first flow equalizing member 2 includes a first plate body 22 and a support ring 23. The first plate body 22 is in the shape of a disc, and the support ring 23 is in the shape of a ring. The first flow equalizing holes 21 are circular holes.

[0100] A plurality of first flow equalizing holes 21 are uniformly arranged on the first plate body 22. The plurality of first flow equalizing holes 21 are arranged in multiple circles, and the plurality of first flow equalizing holes 21 in each circle are arranged at equal intervals in the circumferential direction. The diameter of the first flow equalizing holes 21 in the outer circle is larger than the diameter of the first flow equalizing holes 21 in the inner circle. The distance between two adjacent first flow equalizing holes 21 in the outer circle is larger than the distance between two adjacent first flow equalizing holes 21 in the inner circle.

[0101] The first flow equalizing member 2 is further provided with a first groove 24 extending downward from the plane where the first plate body 22 is located, and the first groove 24 is annular.

[0102] As Figure 3 shown, the second flow equalizing member 3 is in the shape of a cylinder. The second flow equalizing holes 31 are circular holes.

[0103] A plurality of second flow equalizing holes 31 are uniformly arranged on the second flow equalizing member 3. The plurality of second flow equalizing holes 31 are arranged in multiple circles, and the plurality of second flow equalizing holes 31 in each circle are arranged at equal intervals in the circumferential direction. The diameter of the second flow equalizing holes 31 in the outer circle is larger than the diameter of the second flow equalizing holes 31 in the inner circle. The distance between two adjacent second flow equalizing holes 31 in the outer circle is larger than the distance between two adjacent second flow equalizing holes 31 in the inner circle.

[0104] The outer periphery of the second flow equalizing member 3 is provided with a second external thread 32 for cooperating with the second internal thread 153 in the cover body 15 to realize the connection between the second flow equalizing member 3 and the cover body 15.

[0105] The second flow equalizing member 3 has a certain height, and the second flow equalizing member 3 is further provided with a second groove 33 extending downward from the plane where the second flow equalizing holes 31 are located, and the second groove 33 is annular.

[0106] As Figure 4 and Figure 5 shown, the top of the cover body 15 is provided with a convex platform 152 extending downward. The inside of the convex platform 152 is a hollow structure, and the inner wall of the convex platform 152 is provided with a second internal thread 153. There is a gap between the outer wall of the convex platform 152 and the inner wall of the cover body 15, and the top of the container body 14 is inserted into this gap. A sealing ring is provided in this gap.

[0107] The inner wall of the cover body 15 is provided with a first internal thread 151. In the axial direction, the boss 152 is located above the first internal thread 151.

[0108] As Figure 6 shown, the first fixing member 6 is in the shape of a ring. The first fixing member 6 includes a first insertion portion 61 and a first pressing portion 62. The diameter of the first pressing portion 62 is larger than that of the first insertion portion 61. A step is formed on the end face of the first pressing portion 62 close to the first insertion portion 61. When the first insertion portion 61 is inserted into the first groove 24, the edge of the first filter screen 4 can be pressed into the first groove 24, and the step of the first pressing portion 62 presses the main body portion of the first filter screen 4 against the first plate body 22 of the first flow equalizing member 2.

[0109] The structure of the second fixing member 7 can be the same as or different from that of the first fixing member 6.

[0110] When the reactor needs to be used, open the cover body 15, add liver cells into the container body 14, and then seal the container body 14 with the cover body 15; then, convey the nutrient solution into the first accommodation cavity 11 through the first conveying pipe 8. The nutrient solution enters the second accommodation cavity through the inlet 12, and then is evenly distributed through the first flow equalizing member 2, and then enters the first accommodation cavity 11 through the first filter screen 4. The nutrient solution and the liver cells flow evenly in the space between the first flow equalizing member 2 and the second flow equalizing member 3, and then pass through the second flow equalizing member 3 and the second filter screen 5, and finally flow out through the outlet 13 and are conveyed through the second conveying pipe 9.

[0111] In the embodiments of the present invention, the container 1, the first flow equalizing member 2, the second flow equalizing member 3, the first filter screen 4, the second filter screen 5, the first fixing member 6, the second fixing member 7, the first conveying pipe 8, the second conveying pipe 9, etc. can all be prepared from medical polycarbonate materials, which have high transparency, are easy to process, and have good biocompatibility. The sealing ring can be prepared from medical silicone materials, which have good sealing performance and good biocompatibility.

[0112] In the embodiments of the present invention, the container body and the cover body are connected by threads, which is convenient for sterilization and disinfection before use, and the assembly is simple and convenient; by arranging the first filter screen and the second filter screen, the liver cells in the reactor can be prevented from entering the liquid circulation pipeline through the flow equalizing holes; the reactor can provide a stable and uniform flow field distribution for the liver cells, thereby avoiding the problems of cell aggregation and sedimentation and uneven dispersion.

[0113] The embodiments of the present invention solve the problems of uneven culture of liver cells and low mass transfer efficiency in the existing bioartificial liver reactor, and realize the safe short-term culture of liver cells and the efficient transport of metabolic substances.

[0114] The bioartificial liver reactor provided by the present invention can be used in the fields of clinical treatment of liver failure, etc.

[0115] Based on the above-mentioned bioartificial liver reactor, the present invention also provides a bioartificial liver system, which includes the above-mentioned bioartificial liver reactor.

[0116] The positive technical effects of the bioartificial liver reactor in each of the above embodiments are equally applicable to the bioartificial liver system, and will not be elaborated here.

[0117] The descriptions of the above embodiments tend to emphasize the differences between the embodiments. Their similarities can be referred to each other. For the sake of brevity, they will not be elaborated in this article.

[0118] Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them; although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that: without departing from the principle of the present invention, it is still possible to modify the specific implementation manners of the present invention or perform equivalent replacements on some technical features, and these modifications and equivalent replacements should all be covered within the scope of the technical solutions claimed by the present invention.

Claims

1. A bioartificial liver reactor, characterized in that, it includes: a container (1) provided with a first accommodation cavity (11), an inlet (12) communicating with the first accommodation cavity (11) is provided at the first end of the container (1), and an outlet (13) communicating with the first accommodation cavity (11) is provided at the second end of the container (1); a first flow equalizing member (2) disposed inside the first accommodation cavity (11) and adjacent to the inlet (12), and a plurality of uniformly arranged first flow equalizing holes (21) are provided on the first flow equalizing member (2); and a second flow equalizing member (3) disposed inside the first accommodation cavity (11) and adjacent to the outlet (13), and a plurality of uniformly arranged second flow equalizing holes (31) are provided on the second flow equalizing member (3).

2. The bioartificial liver reactor according to claim 1, characterized in that, the first flow equalizing member (2) includes a first plate body (22) and a support ring (23) disposed on one side of the first plate body (22) close to the inlet (12), the first flow equalizing holes (21) are provided on the first plate body (22), the support ring (23) abuts against the inner wall of the first accommodation cavity (11) provided with the inlet (12), and a second accommodation cavity is formed by enclosing the first flow equalizing member (2) and the inner wall of the first accommodation cavity (11) provided with the inlet (12).

3. The bioartificial liver reactor according to claim 2, characterized in that, it further includes a first delivery pipe (8) connected to the inlet (12), and the height of the second accommodation cavity is greater than the length of the first delivery pipe (8) extending into the second accommodation cavity.

4. The bioartificial liver reactor according to claim 1, characterized in that, a plurality of the first flow equalizing holes (21) are arranged radially into a plurality of circles, and the diameter of the first flow equalizing holes (21) located in the outer circle is greater than the diameter of the first flow equalizing holes (21) located in the inner circle; and / or, a plurality of the second flow equalizing holes (31) are arranged radially into a plurality of circles, and the diameter of the second flow equalizing holes (31) located in the outer circle is greater than the diameter of the second flow equalizing holes (31) located in the inner circle.

5. The bioartificial liver reactor according to claim 1, characterized in that, the outer wall of the first flow equalizing member (2) is in close contact with the inner wall of the first accommodation cavity (11) to prevent the first flow equalizing member (2) from moving relative to the first accommodation cavity (11).

6. The bioartificial liver reactor according to claim 1, characterized in that, the container (1) includes a container body (14) and a cover body (15), the cover body (15) is detachably installed on the container body (14), and the internal spaces of the container body (14) and the cover body (15) together form the first accommodation cavity (11).

7. The bioartificial liver reactor according to claim 6, characterized in that, The outer periphery of the container body (14) is provided with a first external thread (141), and the inner wall of the cover body (15) is provided with a first internal thread (151). The container body (14) and the cover body (15) are connected through the cooperation of the first external thread (141) and the first internal thread (151).

8. The bioartificial liver reactor according to claim 6, characterized in that, a boss (152) protruding towards the inside of the first accommodation chamber (11) is provided on the inner wall of the first accommodation chamber (11) where the outlet (13) is provided, and a third accommodation chamber is provided inside the boss (152), and the second flow equalizing member (3) is arranged in the third accommodation chamber.

9. The bioartificial liver reactor according to claim 8, characterized in that, a second internal thread (153) is provided on the inner wall of the third accommodation chamber, a second external thread (32) is provided on the outer periphery of the second flow equalizing member (3), and the second flow equalizing member (3) is installed on the boss (152) through the cooperation of the second external thread (32) and the second internal thread (153).

10. The bioartificial liver reactor according to claim 8, characterized in that, a gap exists between the boss (152) and the inner wall of the cover body (15), and the top of the container body (14) is inserted into the gap.

11. The bioartificial liver reactor according to claim 8, characterized in that, it further includes a sealing ring arranged between the boss (152) and the inner wall of the cover body (15).

12. The bioartificial liver reactor according to claim 1, characterized in that, it further includes a first filter screen (4) arranged on the side of the first flow equalizing member (2) away from the inlet (12), and the first filter screen (4) is configured to block cells located in the first accommodation chamber (11) from flowing out reversely through the inlet (12).

13. The bioartificial liver reactor according to claim 12, characterized in that, it further includes a first fixing member (6). A first groove (24) is provided on the side of the first flow equalizing member (2) away from the inlet (12), and the first fixing member (6) is inserted into the first groove (24) to press the edge of the first filter screen (4) into the first groove (24).

14. The bioartificial liver reactor according to claim 13, characterized in that, the first groove (24) is annular, the first fixing member (6) is annular, and the first fixing member (6) includes a first insertion portion (61) and a first pressing portion (62) arranged along its axis direction. The outer diameter of the first insertion portion (61) is smaller than the outer diameter of the first pressing portion (62). The first insertion portion (61) is inserted into the first groove (24), and the first pressing portion (62) presses against the first flow equalizing member (2).

15. The bioartificial liver reactor according to claim 1, characterized in that, Further included is a second filter screen (5) disposed on a side of the second flow equalizing member (3) close to the outlet (13), and the second filter screen (5) is configured to block cells located in the first accommodation cavity (11) from flowing out through the outlet (13).

16. The bioartificial liver reactor according to claim 15, characterized in that it further includes a second fixing member (7), a second groove (33) is provided on a side of the second flow equalizing member (3) close to the outlet (13), and the second fixing member (7) is inserted into the second groove (33) to press the edge of the second filter screen (5) into the second groove (33).

17. The bioartificial liver reactor according to claim 16, characterized in that the second groove (33) is annular, the second fixing member (7) is annular, and the second fixing member (7) includes a second insertion portion and a second pressing portion arranged along its axial direction, an outer diameter of the second insertion portion is smaller than an outer diameter of the second pressing portion, the second insertion portion is inserted into the second groove (33), and the second pressing portion presses against the second flow equalizing member (3).

18. A bioartificial liver system, characterized in that it includes the bioartificial liver reactor according to any one of claims 1 to 17.