In vitro model culture chips, devices, and dynamic culture systems

Abstract

The embodiments of the present application disclose an in vitro model culture chip, device and dynamic culture system, wherein the chip includes an upper flow channel layer, a lower flow channel layer and an elastic porous membrane, wherein the elastic porous membrane is located at the connection point between the upper flow channel and the lower flow channel to separate the upper flow channel and 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, which forms at least part of the upper flow channel; and / or the lower flow channel layer includes a lower hose, which forms at least part of the lower flow channel. In the present application, when the hose is squeezed, it can form a confined space on one side close to the elastic porous membrane, and move the squeezing position, so as to achieve upward or downward tensile deformation of the elastic porous membrane through the pressure change in the confined space. It can be used to establish an in vitro lung model, an in vitro bladder model, etc., and has great application value in the bioengineering and pharmaceutical industries, reducing the manpower, material and time costs of new drug research and development, and improving the success rate of medication for diseases such as tumors.

Description

Technical Field

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

[0002] The force stimulation of expansion and contraction of organs such as the lungs and bladder in the body is an important factor affecting the growth, differentiation and pathological changes of the organs. Therefore, it is necessary to construct an in vitro model culture device and dynamic culture system based on elastic porous membranes. Summary of the Invention

[0003] The embodiments of the present 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] The present embodiment provides an in vitro model culture chip, comprising:

[0005] an upper flow channel layer, formed with an upper flow channel;

[0006] 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

[0007] an elastic porous membrane, located at the connection point 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;

[0008] Wherein, the upper flow channel layer includes an upper hose, and the upper hose forms at least a portion of the upper flow channel; and / or, the lower flow channel layer includes a lower hose, and the lower hose forms at least a portion of the lower flow channel.

[0009] In some embodiments, the downflow layer comprises:

[0010] A lower flow channel plate assembly, the bottom surface of which is formed with an operation port; and

[0011] The lower hose is connected to the lower flow channel plate assembly and is at least partially located at the operation port.

[0012] In some embodiments, the downflow plate assembly includes:

[0013] a bottom plate, the bottom surface of which is formed with the operation port; and

[0014] The downflow plate is located above the bottom plate and is arranged opposite to the bottom plate. A accommodating cavity is formed between the downflow 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.

[0015] In some embodiments, the accommodating cavities are provided 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.

[0016] In some embodiments, the two accommodating chambers include:

[0017] The first accommodating cavity is provided with a liquid hole on the top surface of the lower flow channel plate, and the liquid hole is communicated with the lower hose in the first accommodating cavity.

[0018] In some embodiments, the two accommodating chambers include:

[0019] 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.

[0020] In some embodiments, 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;

[0021] The lower flow channel plate is formed with two operation ports, and the two lower hoses are arranged in a one-to-one correspondence with the two operation ports.

[0022] In some embodiments, the downflow channel layer is centrally symmetrical about its central axis.

[0023] In some embodiments, a sink connected to the downflow channel is formed on the top surface of the downflow channel layer, and the elastic porous membrane is located in the sink.

[0024] In some embodiments, the in vitro model culture chip further comprises a bracket having a through hole formed thereon, the elastic porous membrane is adhered to the bracket and covers the through hole, and the elastic porous membrane is arranged at the connection point between the upper flow channel and the lower flow channel through the bracket.

[0025] In some embodiments, a sealing ring is formed between the elastic porous membrane and the upper flow channel layer and / or between the elastic porous membrane and the lower flow channel layer, and the sealing ring avoids the connection between the upper flow channel and the lower flow channel.

[0026] In some embodiments, the upper flow channel layer comprises:

[0027] an upper flow channel plate, a bottom surface of which is formed with a communication hole; and

[0028] 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 communicated with the lower flow channel through the communicating hole.

[0029] The present application also provides an in vitro model culture device, comprising:

[0030] frame;

[0031] at least one in vitro model culture chip, located in the frame, with the upper hose and / or the lower hose of the in vitro model culture chip exposed outside the frame; and

[0032] A pressing plate is pressed against the top of the in vitro model culture chip.

[0033] In some embodiments, the in vitro model culture device comprises a plurality of said in vitro model culture devices, and the pressing plate presses against all said in vitro model culture devices.

[0034] The present application also provides a dynamic culture system, including:

[0035] A stretching instrument comprising a base and a stretching mechanism, wherein the stretching mechanism comprises a stretching portion, and the stretching portion is movable relative to the base along a first direction and a second direction; and

[0036] an in vitro model culture chip or an in vitro model culture device, located on the side of the base where the stretching portion is located;

[0037] 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.

[0038] In some embodiments, the dynamic culture system includes a plurality of the in vitro model culture chips, the stretching instrument includes a plurality of the stretching mechanisms, and the plurality of the stretching mechanisms are arranged in a one-to-one correspondence with the plurality of the in vitro model culture chips.

[0039] In some embodiments, the stretching mechanism comprises:

[0040] a slide rail extending along the first direction;

[0041] 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.

[0042] In some embodiments, the stretching portion is a roller, and the roller is rotatably connected to the lifting member.

[0043] In some embodiments, the dynamic culture system further comprises a rocking perfusion apparatus, and the stretching apparatus is disposed on the rocking perfusion apparatus.

[0044] The in vitro model culture chip, device and dynamic culture system of the embodiments of the present application are designed so that at least a portion of at least one of the upper flow channel and the lower flow channel is formed by a hose, so that when the hose is squeezed, it can form a closed space on the side close to the elastic porous membrane, and move the squeezing position to achieve upward or downward stretching deformation of the elastic porous membrane through the pressure change in the closed space.

[0045] The in vitro model culture chip of the embodiment of the present application can be used to establish an in vitro lung model, an in vitro bladder model, etc., and has great application value to the bioengineering and pharmaceutical industries. It can reduce the manpower, material and time costs of new drug research and development, and improve the success rate of medication for diseases such as tumors. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0047] Figure 1 is a schematic diagram of the three-dimensional structure of the in vitro model culture chip provided in some embodiments of the present application;

[0048] Figure 2 yes Figure 1 A schematic diagram of an exploded structure of an in vitro model culture chip is shown;

[0049] Figure 3 yes Figure 1 Another exploded structure schematic diagram of an in vitro model culture chip is shown;

[0050] Figure 4 yes Figure 1 Schematic diagram of the cross-sectional structure of the in vitro model culture chip;

[0051] Figure 5 yes Figure 1 A schematic diagram of a partial cross-sectional structure of an in vitro model culture chip is shown;

[0052] Figure 6 is a schematic diagram of the three-dimensional structure of the in vitro model culture device provided in some embodiments of the present application;

[0053] Figure 7 yes Figure 6 A schematic diagram of the exploded structure of the in vitro model culture device is shown;

[0054] Figure 8 is a schematic diagram of the three-dimensional structure of the dynamic culture system provided in some embodiments of the present application;

[0055] Figure 9 yes Figure 8 Schematic diagram of the explosion structure of the dynamic culture system shown;

[0056] Figure 10 yes Figure 8 Schematic diagram of the cross-sectional structure of the dynamic culture system shown;

[0057] Figure 11 It is a schematic diagram of the three-dimensional structure of the dynamic culture system provided in other embodiments of the present application.

[0058] Description of reference numerals:

[0059] 10. In vitro model culture chip;

[0060] 12. Upper flow channel layer; 121. Upper flow channel; 122. Cover plate; 124. Upper flow channel plate; 1241. Via hole; 1242. Connecting hole;

[0061] 14. Lower flow channel layer; 141. Lower flow channel; 142. Lower hose; 144. Lower flow channel plate assembly; 1442. Operation port; 1444. Bottom plate; 1446. Lower flow channel plate; 1448. Accommodation chamber; 1448a. First accommodation chamber; 1448b. Second accommodation chamber; 1449. Lower flow channel chamber; 1440. Liquid hole; 146. Sink; 148. Lower liquid storage chamber; 140. Cover;

[0062] 16. Elastic porous membrane;

[0063] 18. Bracket; 182. Through hole;

[0064] 19. Sealing ring;

[0065] e, upper culture chamber; f, lower culture chamber;

[0066] 2. In vitro model culture device; 3. Frame; 4. Press plate; 5. Dynamic culture system; 6. Stretching instrument; 602. Base; 604. Stretching mechanism; 6042. Stretching part; 6044. Slide rail; 606. Slot; 608. Chamber; 609. Cavity port; 8. Swinging perfusion instrument; x, first direction; y, second direction. DETAILED DESCRIPTION

[0067] In order to make the objectives, technical solutions and advantages of the present application clearer, the embodiments of the present application will be described in further detail below with reference to the accompanying drawings.

[0068] When the following description refers to the accompanying drawings, unless otherwise indicated, the same numbers in different drawings represent the same or similar elements. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present application. Instead, they are merely examples of devices and methods consistent with certain aspects of the present application, as detailed in the appended claims.

[0069] The force stimulation of expansion and contraction of organs such as the lungs and bladder in the body is an important factor affecting the growth, differentiation and pathological changes of the organs. Therefore, it is necessary to construct an in vitro model culture device and dynamic culture system based on elastic porous membranes.

[0070] There are two related solutions. Solution 1: A passive elastic membrane chip controlled by an air pump. The elastic membrane is driven by a fluctuating gas or liquid pressure, causing the membrane to deform. During the culture process, the culture medium above the membrane remains stationary. A flow path is arranged below the membrane, allowing the culture medium to flow along the membrane surface under external force. Automatic microvalves are located at the inlet and outlet of the flow path below the membrane. Closing these microvalves seals the culture medium below the membrane. The air pump then applies pressure to the culture medium below the membrane, causing the membrane to stretch and deform.

[0071] Option 2: An active elastic membrane chip controlled by an air pump. The elastic membrane is directly stretched or compressed by an external force, achieving deformation of the elastic membrane. The chip body is made of 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 and lower flow channels. Under external force control, the culture medium in the upper and lower flow channels can flow in a forward and backward direction along the surface of the elastic membrane. The elastic membrane is fixed to the side walls of the left and right closed air chambers. The air pump increases or decreases the pressure in the left and right closed air chambers, achieving expansion or contraction of the closed air chambers, thereby driving the elastic membrane to stretch or contract.

[0072] The above-mentioned solution 1 has the following problems: (1) The application scope of the chip is limited: dynamic culture cannot be carried out on the upper side of the elastic membrane, and it is not suitable for constructing complex in vitro biological models; (2) After the chip is used to construct the biological model, its detection method is limited: after the biological model is constructed, the chip needs to be destructively dismantled to be taken out for analysis; (3) The high-throughput control equipment of the gas valve is expensive and the gas valve is easy to damage, resulting in poor equipment stability.

[0073] The above-mentioned solution 2 has the following problems: (1) low throughput; (2) limited biological model detection methods: after the biological model is constructed, the chip needs to be destructively dismantled to remove it for analysis.

[0074] See also Figures 1 to 5 The embodiment of the present application provides an in vitro model culture chip 10 , which includes an upper flow channel layer 12 , a lower flow channel layer 14 and an elastic porous membrane 16 .

[0075] The upper flow channel layer 12 is formed with an upper flow channel 121. The lower flow channel layer 14 is formed with a lower flow channel 141, which is located below and connected to the upper flow channel 121. An elastic porous membrane 16 is located at the connection between 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. The upper flow channel layer 12 includes an upper hose that forms at least a portion of the upper flow channel 121; and / or the lower flow channel layer 14 includes a lower hose 142 that forms at least a portion of the lower flow channel 141.

[0076] In the embodiment of the present application, the upper flow channel layer 12 and the elastic porous membrane 16 form a semi-enclosed upper culture chamber e, while the lower flow channel layer 14 and the elastic porous membrane 16 form a semi-enclosed lower culture chamber f. At least one of the upper flow channel 121 and the lower flow channel 141 is at least partially formed by a flexible tube. When squeezed, the flexible tube forms a sealed space near the elastic porous membrane 16. By shifting the squeeze position, the elastic porous membrane 16 is stretched upward or downward by varying the pressure in the sealed space. Since the flexible tube can deform when squeezed, it can recover when unsqueezed.

[0077] The in vitro model culture chip 10 of the embodiment of the present application can be used to establish an in vitro lung model, an in vitro bladder model, etc., and has great application value to the bioengineering and pharmaceutical industries. It can reduce the manpower, material and time costs of new drug research and development, and improve the success rate of medication for diseases such as tumors.

[0078] After the biological model is constructed, the elastic porous membrane 16 can be taken out for analysis without destructive removal of the chip.

[0079] The lower flow channel layer 14 includes a lower flow channel plate assembly 144 and a lower hose 142. An access port 1442 is formed on the bottom surface of the lower flow channel plate assembly 144. The lower hose 142 is connected to the lower flow channel plate assembly 144 and is at least partially located within the access port 1442. This allows the lower hose 142 to be exposed through the access port 1442, making it easy to access and perform operations such as squeezing the lower hose 142. For example, this allows a tensile tester to pass through the access port 1442 and act on the lower hose 142.

[0080] It should be noted that since the stretching instrument will move the extrusion position on the lower hose 142 after squeezing the lower hose 142, the portion of the lower hose 142 exposed at the operating port 1442 may have a certain length so that the stretching instrument can move and squeeze the lower hose 142.

[0081] In some embodiments, the lower flow plate assembly 144 includes a base plate 1444 and a lower flow plate 1446. An operating port 1442 is formed on the bottom surface of the base plate 1444. The lower flow plate 1446 is located above and opposite the base plate 1444. A receiving cavity 1448 is formed between the lower flow plate 1446 and the base plate 1444. The receiving cavity 1448 communicates with the operating port 1442. A portion of the lower hose 142 is located within the operating port 1442, while the remaining portion is located within the receiving cavity 1448. This facilitates access and squeezing of the portion of the lower hose 142 located within the receiving cavity 1448, while the portion of the lower hose 142 located within the receiving cavity 1448 facilitates securing the lower hose 142 to the lower flow plate assembly 144.

[0082] In some embodiments, the lower hose 142 and the accommodating cavity 1448 may be tightly fitted, so that the lower hose 142 is not easily moved within the accommodating cavity 1448 .

[0083] In some embodiments, the lower hose 142 may be fixed to at least one of the bottom plate 1444 and the lower flow channel plate 1446 by bonding or other methods.

[0084] In some embodiments, the operation port 1442 passes through the top and bottom surfaces of the bottom plate 1444 .

[0085] In some embodiments, the top surface of the bottom plate 1444 is disposed in a groove, which constitutes a receiving cavity 1448 .

[0086] In some embodiments, two opposite sides of the operation port 1442 are provided with accommodating cavities 1448, and the two ends of the lower hose 142 are respectively located in the two accommodating cavities 1448, and the middle of the lower hose 142 is located at the operation port 1442. In this way, both ends of the lower hose 142 can achieve the fixation of the lower hose 142.

[0087] In some embodiments, the two accommodating chambers 1448 include a first accommodating chamber 1448a. The top surface of the lower flow channel plate 1446 is formed with a liquid hole 1440, which is connected to the lower hose 142 in the first accommodating chamber 1448a. The liquid hole 1440 can be used to flow materials into or out of the lower culture chamber f.

[0088] In some embodiments, the lower flow channel layer 14 further includes a lower liquid storage chamber 148 . The lower liquid storage chamber 148 is located above the lower flow channel plate 1446 and communicates with the liquid hole 1440 .

[0089] In some embodiments, the two accommodating chambers 1448 include a second accommodating chamber 1448b. A lower flow channel chamber 1449 is formed between the lower flow channel plate 1446 and the bottom plate 1444. The lower flow channel chamber 1449 communicates with the lower hose 142 within the second accommodating chamber 1448b. The lower flow channel chamber 1449 forms part of the lower flow channel 141 and communicates with the upper flow channel 121. The lower flow channel chamber 1449 is the portion of the lower flow channel 141 that is adjacent to the upper flow channel 121.

[0090] In some embodiments, the bottom plate 1444 has an opening at the bottom of the lower flow channel cavity 1449. The lower flow channel plate assembly 144 also includes a cover 140 located at the opening and sealing the opening. The design of the cover 140 facilitates cleaning and other operations of the lower flow channel 141. The cover 140 can be transparent, facilitating observation of the cell culture conditions within.

[0091] In some embodiments, the lower flow channel layer 14 includes two lower hoses 142, and the lower flow channel 141 is located between the two lower hoses 142 and is connected to the upper flow channel 121. The lower flow channel plate 1446 is formed with two operating ports 1442, and the two lower hoses 142 are arranged in a one-to-one correspondence with the two operating ports 1442. It is understandable that the connection between the upper flow channel 121 and the lower flow channel 141 is located between the two lower hoses 142, and 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 two lower hoses 142 can be respectively acted on by a stretching instrument through the two operating ports 1442 to form a confined space between the parts where the two lower hoses 142 are acted on, and then the elastic porous membrane 16 can be stretched upward or downward by changing the acting part of the stretching instrument on the two lower hoses 142. For example, by changing the active parts of the stretching instrument on the two lower hoses 142 so that the two active parts are separated, the elastic porous membrane 16 can be stretched downward. For another example, by changing the active parts of the stretching instrument on the two lower hoses 142 so that the two active parts are close together, the elastic porous membrane 16 can be stretched upward.

[0092] In some embodiments, the lower flow channel layer 14 is symmetrical about its central axis, which is beneficial for evenly distributing the upward or downward tensile forces on the left and right sides of the elastic porous membrane 16 .

[0093] In summary, the lower flow channel layer 14 includes a cover 140, a bottom plate 1444, a lower flow channel plate 1446, a lower hose 142, and a lower liquid storage chamber 148. During assembly, the lower flow channel layer 14 can be assembled into an integral part.

[0094] In some embodiments, a top surface of the lower flow channel layer 14 is formed with a sink 146 that communicates with the lower flow channel 141, and the elastic porous membrane 16 is located within the sink 146. The design of the sink 146 facilitates assembly. After the elastic porous membrane 16 is assembled within the sink 146 of the lower flow channel layer 14, it is then assembled with the upper flow channel layer 12, thereby improving the assembly alignment accuracy of the elastic porous membrane 16.

[0095] In certain embodiments, the in vitro model culture chip 10 further comprises a support 18, the support 18 being formed with a through hole 182, the elastic porous membrane 16 being fitted with the support 18 and covering the through hole 182, and the elastic porous membrane 16 being arranged at the connection between the upper flow channel 121 and the lower flow channel 141 through the support 18. In this way, the support 18 and the elastic porous membrane 16 can be connected as an elastic porous membrane plug-in, which is connected to the upper flow channel layer 12 and / or the lower flow channel layer 14 in the form of the 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 the need for destructive removal of the chip.

[0096] In some embodiments, after the elastic porous membrane insert 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.

[0097] 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. 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.

[0098] In the embodiment of the present application, a sealing ring 19 is 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 .

[0099] 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 is connected to the lower flow channel 141 through the communication hole 1242.

[0100] 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 .

[0101] In some embodiments, the upper flow channel plate 124 is provided with perforations, and screws pass through the perforations on the upper flow channel plate 124, the perforations on the bottom plate 1444, and the perforations on the lower flow channel plate 1446 to assemble and fix the upper flow channel layer 12 and the lower flow channel layer 14.

[0102] In some embodiments, the upper flow channel plate 124 is provided with a via 1241, and the lower liquid storage chamber 148 passes through the via 1241 and is partially located above the upper flow channel plate 124. With this design, the inner wall of the via 1241 can play a certain role in limiting the lower liquid storage chamber 148, thereby improving the connection reliability between the upper flow channel layer 12 and the lower flow channel layer 14.

[0103] In summary, the upper flow channel layer 12 includes the upper flow channel plate 124 and the cover plate 122. During assembly, the upper flow channel layer 12 can be assembled into an integral part.

[0104] See Figures 6 and 7 The present invention also provides an in vitro model culture device 2, which includes a frame 3, at least one in vitro model culture chip 10, and a pressure plate 4. The in vitro model culture chip 10 is located within the frame 3, and the upper hose and / or lower hose 142 of the in vitro model culture chip 10 are exposed from the frame 3. The pressure plate 4 presses against the top of the in vitro model culture chip 10.

[0105] 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, see Figures 6 and 7 , place six sets of in vitro model culture chips 10 in the frame 3, cover with the pressing plate 4, and use two screws to tighten and fix them into one.

[0106] See Figures 8 to 11 , the embodiment of the present application also provides a dynamic culture system 5, the dynamic culture system 5 includes a stretching instrument 6, an in vitro model culture chip 10 or an in vitro model culture device 2. The stretching instrument 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 along the first direction x and the second direction y relative to the base 602. The in vitro model culture chip 10 and the in vitro model culture device 2 are located on the side of the stretching part 6042 of the base 602. 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 stretching instrument 6 can move along the length direction and radial direction of the upper hose / lower hose 142 to achieve a stretching effect.

[0107] In some embodiments, the first direction x may be along a horizontal direction, and the second direction y may be along a vertical direction.

[0108] In some embodiments, the dynamic culture system 5 includes multiple in vitro model culture chips 10, and the stretching instrument 6 includes multiple stretching mechanisms 604, and the multiple stretching mechanisms 604 are arranged in a one-to-one correspondence with the multiple 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 to achieve 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 stretching instrument 6, and the six sets of stretching mechanisms 604 and the six sets of in vitro model culture chips 10 correspond one-to-one in the vertical direction.

[0109] In some embodiments, the stretching portions 6042 of the plurality of stretching mechanisms 604 may be arranged in a straight line or in an oblique arrangement.

[0110] 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 lower flow channel layer 14 , and each stretching part 6042 corresponds to a lower hose 142 .

[0111] In some embodiments, the stretching mechanism 604 includes a slide rail 6044 and a lifting member (not shown). The slide rail 6044 extends along a first direction x. The lifting member is slidably connected to the slide rail 6044 along the first direction x. The lifting member is connected to the stretching portion 6042 and is used to drive the stretching portion 6042 to move along a second direction y.

[0112] In some embodiments, the stretching portion 6042 is a roller rotatably connected to the lifting member. Thus, when the upper / lower hose 142 moves to the extrusion position, the stretching portion 6042 is in rolling contact with the upper / lower hose 142, thereby reducing friction therebetween and alleviating wear on the upper / lower hose 142.

[0113] In some embodiments, a card slot 606 may be provided on the base 602 of the stretching instrument 6 , and the in vitro model culture chip 10 and the in vitro model culture device 2 may be installed in the card slot 606 .

[0114] In some embodiments, a chamber 608 and a cavity 609 communicating with the chamber 608 may be provided on the base 602 of the stretching instrument 6. The stretching portion 6042 of the stretching mechanism 604 may extend out of the chamber 608 of the base 602 through the cavity 609 and act on the upper hose / lower hose 142.

[0115] In some embodiments, the dynamic culture system 5 further includes a rocking perfusion device 8, and the stretching device 6 is disposed on the rocking perfusion device 8. The stretching device 6 equipped with the in vitro model culture chip 10 or the in vitro model culture device 2 is placed on the rocking perfusion device 8 to form the dynamic culture system 5.

[0116] When using the in vitro model culture device 2 and the dynamic culture system 5, a certain volume of culture medium will be added to the lower culture chamber f. At this time, the stretching mechanism 604 has no contact with the upper hose / lower hose 142, and the in vitro model culture chip 10 is in a rocking perfusion culture state. At the same time, the stretching mechanism 604 is in the stretching waiting position.

[0117] The steps of resetting the elastic porous membrane 16 from the reset state, that is, stretching and deforming upward, to the reset state include:

[0118] In step S21 , the stretching mechanism 604 is in a stretching waiting position.

[0119] In step S22 , the stretching mechanism 604 pushes 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 , so that a closed space is formed between the squeezed points on the two lower hoses 142 .

[0120] In step S23, the two rollers move toward each other from both sides along the slide rail 6044 (in the first direction x), squeezing the culture medium and causing the elastic porous membrane 16 to stretch upward. The stretching device 6 controls the amount of deformation of the elastic porous membrane 16 by controlling the distance the two rollers move toward the center.

[0121] In step S24 , the two rollers move away from each other from the center to the sides along the slide rail 6044 (in the first direction x), and the elastic porous membrane 16 recovers from the upwardly stretched deformed state to the initial state.

[0122] In step S25 , the stretching mechanism 604 is reset downward along the second direction y, the two rollers are separated from the lower hose 142 , the in vitro model culture chip 10 is restored to the rocking perfusion culture state, and the stretching mechanism 604 is in the stretching waiting position.

[0123] The steps of the elastic porous membrane 16 from the reset state - downward stretching deformation - to the reset state include:

[0124] In step S31 , when the stretching mechanism 604 is out of contact with the lower hose 142 , the rollers move closer to each other along the slide rail 6044 (in the first direction x), switching from the stretching waiting position to the contraction waiting position.

[0125] In step S32 , the stretching mechanism 604 pushes 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 , so that a closed space is formed between the squeezed points on the two lower hoses 142 .

[0126] In step S33, the two rollers move away from each other along the slide rail 6044 (in the first direction x), pulling the culture medium, causing the elastic porous membrane 16 to shrink downward. The stretching instrument 6 controls the amount of downward deformation of the elastic porous membrane 16 by controlling the distance the two rollers move.

[0127] In step S34 , the two rollers move closer to each other from both sides toward the center along the slide rail 6044 (in the first direction x), and the elastic porous membrane 16 recovers from the downward contracted deformed state to the initial state.

[0128] In step S35 , the stretching mechanism 604 is reset downward along the second direction y, the two rollers are separated from the lower hose 142 , and the in vitro model culture chip 10 is restored to the rocking perfusion culture state, and the stretching mechanism 604 is in the contraction waiting position.

[0129] In the description of this application, it should be understood that the terms "first", "second", etc. are used for descriptive purposes only and should not be understood as indicating or implying relative importance. For those of ordinary skill in the art, the specific meanings of the above terms in this application can be understood according to the specific circumstances. In addition, in the description of this application, unless otherwise specified, "multiple" refers to at least two, for example, two, three, four, etc. "and / or" describes the association relationship of associated objects, indicating that three relationships may exist. For example, A and / or B can represent: A exists alone, A and B exist at the same time, and B exists alone. The character " / " generally indicates that the previous and subsequent associated objects are in an "or" relationship.

[0130] The above disclosure is only a preferred embodiment of the present application, and certainly cannot be used to limit the scope of rights of the present application. Therefore, equivalent changes made according to the claims of the present application are still 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 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 and the elastic porous membrane form a semi-enclosed upper culture chamber, and the lower flow channel layer and the elastic porous membrane form a semi-enclosed lower culture chamber; Wherein, the upper flow channel layer includes an upper hose, and the upper hose forms at least a portion of the upper flow channel; and / or, the lower flow channel layer includes a lower hose, and the lower hose forms at least a portion of the lower flow channel.

2. The in vitro model culture chip according to claim 1, characterized in that The downflow 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 assembly 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 downflow plate assembly comprises: a bottom plate, the bottom surface of which is formed with the operation port; and The downflow plate is located above the bottom plate and is arranged opposite to the bottom plate. A accommodating cavity is formed between the downflow 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 provided 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 cavity is provided with a liquid hole on the top surface of the lower flow channel plate, and the liquid hole is communicated with the lower hose in the first accommodating cavity.

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 a 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 downflow channel is formed on the top surface of the downflow 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 communication 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 communicated with the lower flow channel through the communicating 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 if the upper flow channel layer of the in vitro model culture chip includes an upper hose, the upper hose is exposed to the frame, and / or, if the lower flow channel layer includes a lower hose, the lower hose is exposed to the frame; as well as, 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 is movable 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; 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: The stretching apparatus comprises a plurality of the in vitro model culture chips, and the stretching apparatus comprises a plurality of the stretching mechanisms, and the plurality of the stretching mechanisms are arranged in a 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 portion 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 with the stretching instrument.

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