In-vitro model culture chip, in-vitro model culture device and dynamic culture system

Abstract

The embodiment of the invention discloses an in-vitro model culture chip, an in-vitro model culture device and a dynamic culture system, the chip comprises an upper flow channel layer, a lower flow channel layer and an elastic porous membrane, the elastic porous membrane is located at the communication position of an upper flow channel and a lower flow channel so as to separate the upper flow channel from the lower flow channel, and an upper culture chamber and a lower culture chamber are formed; wherein the upper runner layer comprises an upper hose, and at least part of an upper runner is formed by the upper hose; and / or the lower runner layer comprises a lower hose, and at least part of the lower runner is formed by the lower hose. When the hose is extruded, the closed space can be formed on the side close to the elastic porous film, the extrusion position is moved, and upward or downward tensile deformation of the elastic porous film is achieved through the pressure intensity change of the closed space. The method can be used for establishing an in-vitro lung model, an in-vitro bladder model and the like, has great application value in bioengineering and pharmaceutical industries, reduces manpower, material and time costs of new drug research and development, and improves the medication success rate of diseases such as tumors.

Description

Technical Field

[0001] This application relates to the field of biomedical engineering technology, and particularly relates to an in vitro model culture chip, device and dynamic culture system. Background Art

[0002] The force stimuli of the expansion and contraction of organs such as the lungs and bladder in the body are important factors affecting the growth, differentiation and lesions of the organs. Therefore, it is necessary to construct an in vitro model culture device and a dynamic culture system based on an elastic porous membrane. Summary of the Invention

[0003] Embodiments of this application provide an in vitro model culture chip, device and dynamic culture system for establishing an in vitro lung model, an in vitro bladder model, etc.

[0004] Embodiments of this application provide an in vitro model culture chip, including: An upper flow channel layer, formed with an upper flow channel; A lower flow channel layer, formed with a lower flow channel, the lower flow channel is located below the upper flow channel and communicated with the upper flow channel; and, An elastic porous membrane, located at the communication part of the upper flow channel and the lower flow channel, to separate the upper flow channel and the lower flow channel, forming an upper culture chamber and a lower culture chamber; Wherein, the upper flow channel layer includes an upper hose, and the upper hose forms at least part of the upper flow channel; and / or, the lower flow channel layer includes a lower hose, and the lower hose forms at least part of the lower flow channel.

[0005] In some embodiments, the lower flow channel layer includes: A lower flow channel plate group, the bottom surface of which is formed with an operation port; and, The lower hose, connecting the lower flow channel plate group and at least part of it is located in the operation port.

[0006] In some embodiments, the lower flow channel plate group includes: A bottom plate, the bottom surface of which is formed with the operation port; and, A lower flow channel plate, located above the bottom plate and arranged opposite to the bottom plate, a receiving cavity is formed between the lower flow channel plate and the bottom plate, the receiving cavity is communicated with the operation port, and part of the lower hose is located in the operation port and the remaining part is located in the receiving cavity.

[0007] In some embodiments, receiving cavities are provided on both opposite sides of the operation port, both ends of the lower hose are respectively located in the two receiving cavities, and the middle part of the lower hose is located in the operation port.

[0008] In some embodiments, the two receiving cavities include: A first accommodation cavity, a liquid hole is formed on the top surface of the downstream channel plate, and the liquid hole is communicated with the lower hose in the first accommodation cavity.

[0009] In some embodiments, the two accommodation cavities include: A second accommodation cavity, a downstream channel cavity is formed between the downstream channel plate and the bottom plate, the downstream channel cavity is communicated with the lower hose in the second accommodation cavity, the downstream channel cavity forms part of the downstream channel, and the downstream channel cavity is communicated with the upstream channel.

[0010] In some embodiments, the downstream channel layer includes two lower hoses, and the part of the downstream channel located between the two lower hoses is communicated with the upstream channel; The downstream channel plate is formed with two operation ports, and the two lower hoses are arranged in one-to-one correspondence with the two operation ports.

[0011] In some embodiments, the downstream channel layer is centrosymmetric about its central axis.

[0012] In some embodiments, a sunken groove communicated with the downstream channel is formed on the top surface of the downstream channel layer, and the elastic porous membrane is located in the sunken groove.

[0013] In some embodiments, the in vitro model culture chip further includes a bracket formed with a through hole, the elastic porous membrane is attached to the bracket and covers the through hole, and the elastic porous membrane is arranged at the communication part between the upstream channel and the downstream channel through the bracket.

[0014] In some embodiments, a sealing ring is formed between the elastic porous membrane and the upstream channel layer and / or between the elastic porous membrane and the downstream channel layer, and the sealing ring avoids the communication part between the upstream channel and the downstream channel.

[0015] In some embodiments, the upstream channel layer includes: An upstream channel plate, a communication hole is formed on its bottom surface; and, A cover plate, located above the upstream channel plate, and an upstream channel is formed between the cover plate and the upstream channel plate, and the upstream channel is communicated with the downstream channel through the communication hole.

[0016] The embodiment of the present application also provides an in vitro model culture device, including: A frame; At least one in vitro model culture chip, located in the frame, and the upper hose and / or the lower hose of the in vitro model culture chip are exposed outside the frame; and, A pressing plate, pressing against the upper part of the in vitro model culture chip.

[0017] In some of these embodiments, an in vitro model culture device includes a plurality of the in vitro model culture devices, and a pressing plate presses against all of the in vitro model culture devices.

[0018] An embodiment of the present application also provides a dynamic culture system, including: A stretcher, including a base and a stretching mechanism. The stretching mechanism includes a stretching part that can move relative to the base in a first direction and a second direction; and, An in vitro model culture chip or an in vitro model culture device, located on the side of the base where the stretching part is located; Wherein, the first direction is along the length direction of the upper hose, and the second direction is along the radial direction of the upper hose; and / or, the first direction is along the length direction of the lower hose, and the second direction is along the radial direction of the lower hose.

[0019] In some of these embodiments, the dynamic culture system includes a plurality of the in vitro model culture chips, the stretcher includes a plurality of the stretching mechanisms, and the plurality of stretching mechanisms are arranged in one-to-one correspondence with the plurality of in vitro model culture chips.

[0020] In some of these embodiments, the stretching mechanism includes: A slide rail extending in the first direction; A lifting member slidably connected to the slide rail in the first direction. The lifting member is connected to the stretching part and is used to drive the stretching part to move in the second direction.

[0021] In some of these embodiments, the stretching part is a roller, and the roller is rotatably connected to the lifting member.

[0022] In some of these embodiments, the dynamic culture system further includes a rocking perfusion apparatus, and the stretcher is arranged on the rocking perfusion apparatus.

[0023] In the in vitro model culture chip, device and dynamic culture system according to the embodiments of the present application, at least part of at least one of the upstream channel and the downstream channel is formed by a hose in the design, so that when the hose is squeezed, a sealed space can be formed on the side close to the elastic porous membrane, and the squeezing position can be moved. Through the pressure change in the sealed space, upward or downward stretching deformation of the elastic porous membrane is achieved.

[0024] The in vitro model culture chip according to the embodiments of the present application can be used to establish in vitro lung models, in vitro bladder models, etc., and has great application value in the fields of bioengineering and the pharmaceutical industry. It can reduce the human, material and time costs of new drug research and development, and improve the success rate of drug use for diseases such as tumors. Description of the Drawings

[0025] To more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the accompanying drawings required for the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only some embodiments of the present application. For those of ordinary skill in the art, without creative efforts, other accompanying drawings can be obtained based on these drawings.

[0026] Figure 1 It is a schematic three-dimensional structure diagram of an in vitro model culture chip provided by some embodiments of the present application; Figure 2 is Figure 1 An exploded structure diagram of the in vitro model culture chip shown; Figure 3 is Figure 1 Another exploded structure diagram of the in vitro model culture chip shown; Figure 4 is Figure 1 A schematic cross-sectional structure diagram of the in vitro model culture chip shown; Figure 5 is Figure 1 A partial cross-sectional structure diagram of the in vitro model culture chip shown; Figure 6 It is a schematic three-dimensional structure diagram of an in vitro model culture device provided by some embodiments of the present application; Figure 7 is Figure 6 An exploded structure diagram of the in vitro model culture device shown; Figure 8 It is a schematic three-dimensional structure diagram of a dynamic culture system provided by some embodiments of the present application; Figure 9 is Figure 8 An exploded structure diagram of the dynamic culture system shown; Figure 10 is Figure 8 A schematic cross-sectional structure diagram of the dynamic culture system shown; Figure 11 It is a schematic three-dimensional structure diagram of a dynamic culture system provided by some other embodiments of the present application.

[0027] Explanation of reference numerals: 10. In vitro model culture chip; 12. Upstream channel layer; 121. Upstream channel; 122. Cover plate; 124. Upstream channel plate; 1241. Through hole; 1242. Communication hole; 14. Lower flow channel layer; 141. Lower flow channel; 142. Lower hose; 144. Lower flow channel plate group; 1442. Operation port; 1444. Bottom plate; 1446. Lower flow channel plate; 1448. Accommodation cavity; 1448a. First accommodation cavity; 1448b. Second accommodation cavity; 1449. Lower flow channel cavity; 1440. Liquid hole; 146. Sunk groove; 148. Lower liquid storage chamber; 140. Sealing cover; 16. Elastic porous membrane; 18. Bracket; 182. Through hole; 19. Sealing ring; e. Upper culture chamber; f. Lower culture chamber; 2. In vitro model culture device; 3. Frame; 4. Pressing plate; 5. Dynamic culture system; 6. Tensile instrument; 602. Base; 604. Tensile mechanism; 6042. Tensile part; 6044. Slide rail; 606. Card slot; 608. Chamber; 609. Chamber opening; 8. Swing perfusion instrument; x. First direction; y. Second direction. Detailed implementation manners

[0028] To make the objectives, technical solutions, and advantages of this application clearer, the following will further describe in detail the embodiments of this application with reference to the accompanying drawings.

[0029] When the following description relates to the accompanying drawings, unless otherwise indicated, the same numbers in different drawings represent the same or similar elements. The implementation manners described in the following exemplary embodiments do not represent all implementation manners consistent with this application. On the contrary, they are merely examples of devices and methods consistent with some aspects of this application as detailed in the appended claims.

[0030] The force stimulation of the expansion and contraction of organs such as the lungs and bladder in the body is an important factor affecting the growth, differentiation, and lesion of the organs. Therefore, it is necessary to construct an in vitro model culture device and a dynamic culture system based on an elastic porous membrane.

[0031] There are the following two solutions in the related technologies. Solution 1: A passive elastic membrane chip controlled by an air pump. The elastic membrane is driven by gas or liquid with pressure changes to achieve the deformation of the elastic membrane. During the culture process, the culture medium above the elastic membrane remains stationary, and a flow path is arranged below the elastic membrane. The culture medium can flow along the surface of the elastic membrane under external control. Automatic micro valves are arranged at the inlet and outlet of the flow path below the elastic membrane. After closing the micro valves at the inlet and outlet, the culture medium below the elastic membrane is sealed, and the air pump is used to pressurize the culture medium below the elastic membrane, thereby driving the elastic membrane to stretch and deform.

[0032] Solution 2: An active elastic membrane chip controlled by an air pump. The elastic membrane is directly stretched or compressed by an external force to achieve deformation of the elastic membrane. The chip body is made of an elastic material. Inside the chip, an upper flow channel layer, a lower flow channel layer, and left and right closed air chambers are arranged around an elastic membrane. The elastic membrane separates the upper flow channel layer and the lower flow channel layer. Under the control of an external force, the culture medium in the upper and lower flow channel layers can flow back and forth along the surface of the elastic membrane. The elastic membrane is fixed on the side walls of the left and right closed air chambers. By means of an air pump, pressure is added or subtracted to the left and right closed air chambers to achieve expansion or contraction of the closed air chambers, thereby driving the elastic membrane to stretch or contract and deform.

[0033] The above Solution 1 has the following problems: (1) The application range of the chip is limited: Dynamic culture cannot be carried out on the upper side of the elastic membrane, which is not suitable for constructing complex in vitro biological models; (2) After the chip is used to construct a biological model, its detection method is limited: When the biological model is taken out for analysis after construction, the chip needs to be destructively removed; (3) The high-throughput control device for air valves is costly and the air valves are easily damaged, resulting in poor stability of the device.

[0034] The above Solution 2 has the following problems: (1) Low throughput; (2) The detection method of the biological model is limited: When the biological model is taken out for analysis after construction, the chip needs to be destructively removed.

[0035] Please refer to Figures 1 to 5 , an in vitro model culture chip 10 is provided in an embodiment of the present application, including an upper flow channel layer 12, a lower flow channel layer 14, and an elastic porous membrane 16.

[0036] An upper flow channel 121 is formed in the upper flow channel layer 12. A lower flow channel 141 is formed in the lower flow channel layer 14. The lower flow channel 141 is located below the upper flow channel 121 and communicates with the upper flow channel 121. The elastic porous membrane 16 is located at the connection of the upper flow channel 121 and the lower flow channel 141 to separate the upper flow channel 121 and the lower flow channel 141, forming an upper culture chamber e and a lower culture chamber f. Among them, the upper flow channel layer 12 includes an upper flexible tube, and the upper flexible tube forms at least part of the upper flow channel 121; and / or, the lower flow channel layer 14 includes a lower flexible tube 142, and the lower flexible tube 142 forms at least part of the lower flow channel 141.

[0037] In an embodiment of the present application, the upper flow channel layer 12 and the elastic porous membrane 16 form a semi-closed upper culture chamber e, and the lower flow channel layer 14 and the elastic porous membrane 16 form a semi-closed lower culture chamber f. Among them, at least part of at least one of the upper flow channel 121 and the lower flow channel 141 is formed by a flexible tube, so that when the flexible tube is squeezed, a closed space can be formed on the side close to the elastic porous membrane 16, and the squeezing position can be moved. Through the pressure change of the closed space, upward or downward stretching deformation of the elastic porous membrane 16 is achieved. Since the flexible tube can be deformed when squeezed and can recover when not squeezed.

[0038] The in-vitro model culture chip 10 according to the embodiments of the present application can be used to establish in-vitro lung models, in-vitro bladder models, etc., and has great application value in the fields of bioengineering and the pharmaceutical industry. It can reduce the human, material and time costs of new drug research and development and improve the success rate of drug use for diseases such as tumors.

[0039] After the biological model is constructed, the elastic porous membrane 16 can be taken out for analysis without destructively dismantling the chip.

[0040] The downstream channel layer 14 includes a downstream channel plate group 144 and a lower hose 142. An operation port 1442 is formed on the bottom surface of the downstream channel plate group 144. The lower hose 142 is connected to the downstream channel plate group 144 and is at least partially located at the operation port 1442. In this way, the lower hose 142 can be exposed through the operation port 1442, facilitating access to the lower hose 142 and performing operations such as squeezing on the lower hose 142. For example, it is convenient for a tensiometer to pass through the operation port 1442 and act on the lower hose 142.

[0041] It should be noted that since the tensiometer will move the squeezing position on the lower hose 142 after squeezing the lower hose 142, the part of the lower hose 142 exposed outside the operation port 1442 can have a certain length so that the tensiometer can move and squeeze the lower hose 142.

[0042] In some embodiments, the downstream channel plate group 144 includes a bottom plate 1444 and a downstream channel plate 1446. The operation port 1442 is formed on the bottom surface of the bottom plate 1444. The downstream channel plate 1446 is located above the bottom plate 1444 and is disposed opposite to the bottom plate 1444. A receiving cavity 1448 is formed between the downstream channel plate 1446 and the bottom plate 1444. The receiving cavity 1448 is communicated with the operation port 1442. A part of the lower hose 142 is located at the operation port 1442, and the remaining part is located in the receiving cavity 1448. In this way, the part of the lower hose 142 located at the operation port 1442 is conducive to being touched and squeezed, and the part of the lower hose 142 located in the receiving cavity 1448 is conducive to fixing the lower hose 142 on the downstream channel plate group 144.

[0043] In some embodiments, a tight fit can be provided between the lower hose 142 and the receiving cavity 1448, so that the lower hose 142 is not easily moved in the receiving cavity 1448.

[0044] In some embodiments, the lower hose 142 can be fixed to at least one of the bottom plate 1444 and the downstream channel plate 1446 by bonding or the like.

[0045] In some embodiments, the operation port 1442 penetrates the top surface and the bottom surface of the bottom plate 1444.

[0046] In some embodiments, a groove is provided on the top surface of the bottom plate 1444, and the groove constitutes the receiving cavity 1448.

[0047] In some embodiments, receiving cavities 1448 are provided on both opposite sides of the operation port 1442. Both ends of the lower hose 142 are respectively located in the two receiving cavities 1448, and the middle part of the lower hose 142 is located at the operation port 1442. In this way, the two ends of the lower hose 142 can both achieve the fixation of the lower hose 142.

[0048] In some embodiments, the two receiving cavities 1448 include a first receiving cavity 1448a. Liquid holes 1440 are formed on the top surface of the downstream flow channel plate 1446, and the liquid holes 1440 communicate with the lower hose 142 in the first receiving cavity 1448a. The liquid holes 1440 can be used for the inflow or outflow of substances in the lower culture chamber f.

[0049] In some embodiments, the downstream flow channel layer 14 further includes a lower liquid storage chamber 148. The lower liquid storage chamber 148 is located above the downstream flow channel plate 1446 and communicates with the liquid holes 1440.

[0050] In some embodiments, the two receiving cavities 1448 include a second receiving cavity 1448b. A downstream flow channel cavity 1449 is formed between the downstream flow channel plate 1446 and the bottom plate 1444. The downstream flow channel cavity 1449 communicates with the lower hose 142 in the second receiving cavity 1448b. The downstream flow channel cavity 1449 forms part of the downstream flow channel 141, and the downstream flow channel cavity 1449 communicates with the upstream flow channel 121. Among them, the downstream flow channel cavity 1449 is the part of the downstream flow channel 141 close to the upstream flow channel 121.

[0051] In some embodiments, the bottom plate 1444 is provided with an opening at the bottom of the downstream flow channel cavity 1449. The downstream flow channel plate group 144 further includes a cover 140 located at the opening and closing the opening. The design of the cover 140 is beneficial for cleaning and other treatments of the downstream flow channel 141. The cover 140 can be a transparent cover, which is beneficial for observing the cell culture situation inside.

[0052] In some embodiments, the downstream channel layer 14 includes two lower hoses 142. The part of the downstream channel 141 located between the two lower hoses 142 communicates with the upstream channel 121. The downstream channel plate 1446 is formed with two operation ports 1442, and the two lower hoses 142 are arranged in one-to-one correspondence with the two operation ports 1442. It can be understood that the connection between the upstream channel 121 and the downstream channel 141 is located between the two lower hoses 142, so the elastic porous membrane 16 is located between the two lower hoses 142. In this way, when the elastic porous membrane 16 is stretched upward or downward, the stretching instrument can act on the two lower hoses 142 through the two operation ports 1442 respectively, so that a sealed space is formed between the parts of the two lower hoses 142 that are acted on. Then, by changing the acting parts of the stretching instrument on the two lower hoses 142, the elastic porous membrane 16 can be stretched upward or downward. For example, by changing the acting parts of the stretching instrument on the two lower hoses 142 to make the two acting parts move away from each other, the downward stretching deformation of the elastic porous membrane 16 can be realized. For another example, by changing the acting parts of the stretching instrument on the two lower hoses 142 to make the two acting parts approach each other, the upward stretching deformation of the elastic porous membrane 16 can be realized.

[0053] In some embodiments, the downstream channel layer 14 is centrosymmetric about its central axis. In this way, it is beneficial to the balanced distribution of the upward or downward stretching forces received by the left and right sides of the elastic porous membrane 16.

[0054] In summary, the downstream channel layer 14 includes a cover 140, a bottom plate 1444, a downstream channel plate 1446, lower hoses 142 and a lower liquid storage chamber 148. During assembly, the downstream channel layer 14 can be first assembled into a single piece.

[0055] In some embodiments, a sink 146 communicating with the downstream channel 141 is formed on the top surface of the downstream channel layer 14, and the elastic porous membrane 16 is located in the sink 146. The design of the sink 146 is convenient for assembly. After the elastic porous membrane 16 is assembled in the sink 146 of the downstream channel layer 14, it can be assembled with the upstream channel layer 12 together, which is beneficial to improving the assembly alignment accuracy of the elastic porous membrane 16.

[0056] In some embodiments, the in vitro model culture chip 10 further includes a bracket 18. The bracket 18 is formed with a through hole 182. The elastic porous membrane 16 is attached to the bracket 18 and covers the through hole 182. The elastic porous membrane 16 is arranged at the connection between the upstream channel 121 and the downstream channel 141 through the bracket 18. In this way, the bracket 18 and the elastic porous membrane 16 can be connected as an elastic porous membrane plug-in, and can be connected to the upstream channel layer 12 and / or the downstream channel layer 14 in the form of an elastic porous membrane plug-in, and the connection is more convenient. After the biological model is constructed, the elastic porous membrane 16 can be taken out for analysis without destructive disassembly of the chip.

[0057] In some embodiments, after the elastic porous membrane plug-in is assembled between the upper flow channel layer 12 and the lower flow channel layer 14, the upper flow channel layer 12 and the lower flow channel layer 14 can be assembled and fixed by two screws.

[0058] In some embodiments, a sealing ring 19 is provided between the elastic porous membrane 16 and the upper flow channel layer 12 and / or between the elastic porous membrane 16 and the lower flow channel layer 14, and the sealing ring 19 avoids the connection between the upper flow channel 121 and the lower flow channel 141. The sealing ring 19 can improve the sealing performance between the upper flow channel 121 and the lower flow channel 141.

[0059] In the embodiments of the present application, sealing rings 19 are provided between the elastic porous membrane 16 and the upper flow channel layer 12 and between the elastic porous membrane 16 and the lower flow channel layer 14.

[0060] In some embodiments, the upper flow channel layer 12 includes an upper flow channel plate 124 and a cover plate 122. A communication hole 1242 is formed on the bottom surface of the upper flow channel plate 124. The cover plate 122 is located above the upper flow channel plate 124, and an upper flow channel 121 is formed between the cover plate 122 and the upper flow channel plate 124. The upper flow channel 121 communicates with the lower flow channel 141 through the communication hole 1242.

[0061] In some embodiments, a groove is provided on the top surface of the upper flow channel plate 124, and the groove forms the upper flow channel 121.

[0062] In some embodiments, through holes are provided on the upper flow channel plate 124, and screws pass through the through holes on the upper flow channel plate 124, the through holes on the bottom plate 1444, and the through holes of the lower flow channel plate 1446 to realize the assembly and fixation of the upper flow channel layer 12 and the lower flow channel layer 14.

[0063] In some embodiments, a through hole 1241 is provided on the upper flow channel plate 124, and the lower liquid storage chamber 148 passes through the through hole 1241 and is partially located above the upper flow channel plate 124. Designed in this way, the inner wall of the through hole 1241 can play a certain limiting role on the lower liquid storage chamber 148 and improve the connection reliability between the upper flow channel layer 12 and the lower flow channel layer 14.

[0064] In summary, the upper flow channel layer 12 includes an upper flow channel plate 124 and a cover plate 122. During assembly, the upper flow channel layer 12 can be first assembled into a single piece.

[0065] Refer to Figures 6 to 7 , embodiments of the present application further provide an in vitro model culture device 2. The in vitro model culture device 2 includes a frame 3, at least one in vitro model culture chip 10, and a pressing plate 4. The in vitro model culture chip 10 is located inside the frame 3, and the upper hose and / or the lower hose 142 of the in vitro model culture chip 10 are exposed outside the frame 3. The pressing plate 4 presses against the upper part of the in vitro model culture chip 10.

[0066] In some embodiments, the in vitro model culture device 2 includes a plurality of in vitro model culture chips 10, and the pressing plate 4 presses against all the in vitro model culture chips 10. For example, referring to Figures 6 to 7 , six sets of in vitro model culture chips 10 are placed in the frame 3. After covering the pressing plate 4, two screws are used to tighten and fix them into one body.

[0067] Referring to Figures 8 to 11 , an embodiment of the present application further provides a dynamic culture system 5. The dynamic culture system 5 includes a stretcher 6, an in vitro model culture chip 10 or an in vitro model culture device 2. The stretcher 6 includes a base 602 and a stretching mechanism 604. The stretching mechanism 604 includes a stretching part 6042, and the stretching part 6042 can move relative to the base 602 along a first direction x and a second direction y. The in vitro model culture chip 10 and the in vitro model culture device 2 are located on the side of the base 602 where the stretching part 6042 is located. Among them, the first direction x is along the length direction of the upper hose, and the second direction y is along the radial direction of the upper hose; and / or, the first direction x is along the length direction of the lower hose 142, and the second direction y is along the radial direction of the lower hose 142. The stretching part 6042 of the stretcher 6 can move along the length direction and the radial direction of the upper hose / lower hose 142 to achieve a stretching effect.

[0068] In some embodiments, the first direction x may be along the horizontal direction, and the second direction y may be along the vertical direction.

[0069] In some embodiments, the dynamic culture system 5 includes a plurality of in vitro model culture chips 10, and the stretcher 6 includes a plurality of stretching mechanisms 604. The plurality of stretching mechanisms 604 are arranged in one-to-one correspondence with the plurality of in vitro model culture chips 10. Each stretching mechanism 604 is used to squeeze the upper hose / lower hose 142 in the corresponding in vitro model culture chip 10 and move the squeezing position, so as to realize the upward or downward stretching deformation of the elastic porous membrane 16 in the corresponding in vitro model culture chip 10. For example, six sets of stretching mechanisms 604 are arranged in the stretcher 6, and the six sets of stretching mechanisms 604 and the six sets of in vitro model culture chips 10 are in one-to-one correspondence in the vertical direction.

[0070] In some embodiments, the stretching parts 6042 of the plurality of stretching mechanisms 604 may be arranged in a straight line or in an inclined manner.

[0071] In some embodiments, the number of stretching parts 6042 included in each stretching mechanism 604 is equal to the number of lower hoses 142 included in the downstream channel layer 14, and each stretching part 6042 corresponds to a lower hose 142.

[0072] In some embodiments, the stretching mechanism 604 includes a slide rail 6044 and a lifting member (not shown in the figure). The slide rail 6044 extends along the first direction x. The lifting member is slidably connected to the slide rail 6044 along the first direction x, and the lifting member is connected to the stretching portion 6042 for driving the stretching portion 6042 to move along the second direction y.

[0073] In some embodiments, the stretching portion 6042 is a roller, and the roller is rotatably connected to the lifting member. In this way, when the stretching portion 6042 moves to the position where the upper hose / lower hose 142 is squeezed, it is in rolling contact with the upper hose / lower hose 142, reducing the friction between the two and reducing the wear of the upper hose / lower hose 142.

[0074] In some embodiments, a card slot 606 may be provided on the base 602 of the stretcher 6, and the in vitro model culture chip 10 and the in vitro model culture device 2 can be loaded into the card slot 606.

[0075] In some embodiments, a chamber 608 and a chamber opening 609 communicating with the chamber 608 may be provided on the base 602 of the stretcher 6. The stretching portion 6042 of the stretching mechanism 604 can extend out of the chamber 608 of the base 602 through the chamber opening 609 and act on the upper hose / lower hose 142.

[0076] In some embodiments, the dynamic culture system 5 further includes a rocking perfusion device 8, and the stretcher 6 is disposed on the rocking perfusion device 8. Placing the stretcher 6 equipped with the in vitro model culture chip 10 or the in vitro model culture device 2 on the rocking perfusion device 8 forms the dynamic culture system 5.

[0077] When using the in vitro model culture device 2 and the dynamic culture system 5, a certain volume of culture medium is added to the lower culture chamber f. At this time, the stretching mechanism 604 is not in contact with the upper hose / lower hose 142, the in vitro model culture chip 10 is in a rocking perfusion culture state, and at the same time, the stretching mechanism 604 is in a stretching waiting position.

[0078] The steps of the elastic porous membrane 16 from the reset state ---- upward stretching deformation ---- reset state include: Step S21, the stretching mechanism 604 is in the stretching waiting position.

[0079] Step S22, the stretching mechanism 604 jacks up along the second direction y, and the two rollers on the slide rail 6044 respectively squeeze and deform the two lower hoses 142 in the in vitro model culture chip 10, causing a closed space to be formed between the squeezed points on the two lower hoses 142.

[0080] Step S23: The two rollers move closer to each other from both sides along the slide rail 6044 (in the first direction x), squeezing the culture medium, causing the elastic porous membrane 16 to be stretched and deformed upward. The stretcher 6 controls the amount of deformation of the elastic porous membrane 16 stretched upward by controlling the stroke of the two rollers moving towards the middle.

[0081] Step S24: The two rollers move away from each other from the middle along the slide rail 6044 (in the first direction x), and the elastic porous membrane 16 returns from the upward stretched and deformed state to the initial state.

[0082] Step S25: The stretching mechanism 604 resets downward along the second direction y, the two rollers disengage from the lower hose 142, and the in vitro model culture chip 10 returns to the rocking perfusion culture state, and the stretching mechanism 604 is in the stretching waiting position.

[0083] The steps of the elastic porous membrane 16 from the reset state ---- downward stretching and deformation ---- reset state include: Step S31: When the stretching mechanism 604 disengages from the lower hose 142, the rollers move closer to each other along the slide rail 6044 (in the first direction x), and switch from the stretching waiting position to the contraction waiting position.

[0084] Step S32: The stretching mechanism 604 jacks up upward along the second direction y, and the two rollers on the slide rail 6044 squeeze and deform the two lower hoses 142 in the in vitro model culture chip 10 respectively, causing a closed space to be formed between the squeezed points on the two lower hoses 142.

[0085] Step S33: The two rollers move away from each other from the middle along the slide rail 6044 (in the first direction x), pumping the culture medium, causing the elastic porous membrane 16 to contract and deform downward. The stretcher 6 controls the amount of deformation of the elastic porous membrane 16 contracting downward by controlling the stroke of the two rollers moving towards the two sides.

[0086] Step S34: The two rollers move closer to each other from both sides along the slide rail 6044 (in the first direction x), and the elastic porous membrane 16 returns from the downward contracted and deformed state to the initial state.

[0087] Step S35: The stretching mechanism 604 resets downward along the second direction y, the two rollers disengage from the lower hose 142, and the in vitro model culture chip 10 returns to the rocking perfusion culture state, and the stretching mechanism 604 is in the contraction waiting position.

[0088] In the description of the present application, it should be understood that the terms "first", "second", etc. are only for descriptive purposes and cannot be construed as indicating or implying relative importance. For those of ordinary skill in the art, the specific meanings of the above terms in the present application can be understood according to specific circumstances. In addition, in the description of the present application, unless otherwise specified, "a plurality of" means at least two, for example, two, three, four, etc. "And / or" describes the association relationship of associated objects and indicates that three relationships can exist. For example, A and / or B can mean: A exists alone, A and B exist simultaneously, and B exists alone. The character " / " generally indicates that the associated objects before and after are in an "or" relationship.

[0089] The above-disclosed are only the preferred embodiments of the present application, and of course, the scope of rights of the present application cannot be limited thereby. Therefore, equivalent changes made according to the claims of the present application still fall within the scope covered by the present application.

Claims

1. An in vitro model culture chip, characterized in that: include: an upper flow channel layer, formed with an upper flow channel; a lower flow channel layer, formed with a lower flow channel, the lower flow channel being located below the upper flow channel and communicating with the upper flow channel; and, an elastic porous membrane, located at the connection between the upper flow channel and the lower flow channel, so as to separate the upper flow channel from the lower flow channel to form an upper culture chamber and a lower culture chamber; Wherein, the upper flow channel layer includes an upper hose, and the upper hose forms at least a part of the upper flow channel; and / or, the lower flow channel layer includes a lower hose, and the lower hose forms at least a part of the lower flow channel.

2. The in vitro model culture chip according to claim 1, characterized in that: The lower flow channel layer comprises: A lower flow channel plate assembly, the bottom surface of which is formed with an operation port; and, The lower hose is connected to the lower flow channel plate group and is at least partially located at the operation port.

3. The in vitro model culture chip according to claim 2, characterized in that: The lower flow channel plate assembly comprises: a bottom plate, the bottom surface of which is formed with the operation port; and The lower flow channel plate is located above the bottom plate and is arranged opposite to the bottom plate. A accommodating cavity is formed between the lower flow channel plate and the bottom plate. The accommodating cavity is connected to the operation port. Part of the lower hose is located at the operation port, and the remaining part is located in the accommodating cavity.

4. The in vitro model culture chip according to claim 3, characterized in that: The accommodating cavities are disposed on opposite sides of the operation port, the two ends of the lower hose are respectively located in the two accommodating cavities, and the middle portion of the lower hose is located at the operation port.

5. The in vitro model culture chip according to claim 4, characterized in that: The two accommodating chambers include: The first accommodating chamber, the top surface of the lower flow channel plate is formed with a liquid hole, and the liquid hole is communicated with the lower hose in the first accommodating chamber.

6. The in vitro model culture chip according to claim 4, characterized in that: The two accommodating chambers include: A second accommodating chamber, a lower flow channel chamber is formed between the lower flow channel plate and the bottom plate, the lower flow channel chamber is communicated with the lower hose in the second accommodating chamber, the lower flow channel chamber forms part of the lower flow channel, and the lower flow channel chamber is communicated with the upper flow channel.

7. The in vitro model culture chip according to any one of claims 2 to 6, characterized in that: The lower flow channel layer includes two lower hoses, and the lower flow channel is located between the two lower hoses and is connected to the upper flow channel; The lower flow channel plate is formed with two operation ports, and the two lower hoses are arranged in one-to-one correspondence with the two operation ports.

8. The in vitro model culture chip according to claim 7, characterized in that: The lower flow channel layer is centrally symmetrical about its central axis.

9. The in vitro model culture chip according to claim 1, characterized in that: A sinking groove communicating with the lower flow channel is formed on the top surface of the lower flow channel layer, and the elastic porous membrane is located in the sinking groove.

10. The in vitro model culture chip according to claim 1, characterized in that: The upper flow channel layer comprises: An upper flow channel plate, a bottom surface of which is formed with a communicating hole; and The cover plate is located above the upper flow channel plate, and the upper flow channel is formed between the cover plate and the upper flow channel plate. The upper flow channel is connected with the lower flow channel through the connecting hole.

11. An in vitro model culture device, characterized in that: include: frame; At least one in vitro model culture chip according to any one of claims 1 to 10 is located in the frame, and the upper hose and / or the lower hose of the in vitro model culture chip is exposed from the frame; and A pressing plate is pressed against the top of the in vitro model culture chip.

12. A dynamic culture system, characterized in that: include: A stretching instrument, comprising a base and a stretching mechanism, wherein the stretching mechanism comprises a stretching portion, and the stretching portion can move relative to the base along a first direction and a second direction; and The in vitro model culture chip according to any one of claims 1 to 10 or the in vitro model culture device according to claim 11, located on the side of the base where the stretching portion is located; Wherein, the first direction is along the length direction of the upper hose, and the second direction is along the radial direction of the upper hose; and / or, the first direction is along the length direction of the lower hose, and the second direction is along the radial direction of the lower hose.

13. The dynamic culture system according to claim 12, characterized in that: It comprises a plurality of the in vitro model culture chips, and the stretching instrument comprises a plurality of the stretching mechanisms, and the plurality of the stretching mechanisms are arranged in one-to-one correspondence with the plurality of the in vitro model culture chips.

14. The dynamic culture system according to claim 12, characterized in that: The stretching mechanism comprises: A slide rail extending along the first direction; A lifting member is slidably connected to the slide rail along the first direction, and the lifting member is connected to the stretching part to drive the stretching part to move along the second direction.

15. The dynamic culture system according to claim 14, characterized in that: The stretching part is a roller, and the roller is rotatably connected to the lifting member.

16. The dynamic culture system according to any one of claims 12 to 15, characterized in that: Also includes: The swing perfusion instrument is provided on the stretching instrument.

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