Perfusion culture box and organ chip culture equipment

Abstract

The invention provides a perfusion culture box and organ chip culture equipment, and relates to the technical field of organ chips. The perfusion culture box comprises a base and a box body, wherein the base is suitable for arranging an organ chip; the box body is arranged on the base, an airflow channel and a liquid chamber are arranged in the box body, the liquid chamber is suitable for storing a culture solution, the liquid chamber is used for being communicated with a culture channel of the organ chip, the airflow channel is used for being communicated with a breathing chamber of the organ chip, and the airflow channel and the liquid chamber are both suitable for being communicated with an external pressure supply device. According to the perfusion culture box and the organ chip culture equipment, the probability that the culture solution and the organ chip are polluted is reduced, and a more appropriate culture environment is provided for the organ chip.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organ chip, and particularly to a perfusion culture box and an organ chip culture device. BACKGROUND

[0002] An organ chip is a microfluidic device that can simulate the function of human organs and create an environment similar to that in the human body, and is used for disease research, new drug discovery and testing, and personalized treatment method exploration. The organ chip needs to be cultured in a specific culture device.

[0003] In the prior art, the culture device of the organ chip includes a culture liquid box and a chip support, the culture liquid box is used for storing culture liquid, and the chip support is used for fixing the organ chip. The organ chip is communicated with the culture liquid box through a delivery pipe, so that the culture liquid is injected into the inside of the organ chip.

[0004] However, the above culture device needs to manually disassemble and assemble the delivery pipe, and the disassembly and assembly process may contaminate the delivery pipe and thus contaminate the culture liquid, affecting the culture environment of the organ chip. SUMMARY

[0005] The present application provides a perfusion culture box and an organ chip culture device, which can reduce the possibility of contamination during the culture of the organ chip.

[0006] In one aspect, the present application provides a perfusion culture box, the organ chip is provided with a culture channel and a breathing chamber, and the perfusion culture box comprises a base, the base is suitable for arranging the organ chip; a box body, the box body is arranged on the base, the box body is provided with an airflow channel and a liquid chamber, the liquid chamber is suitable for storing culture liquid, the liquid chamber is used for communicating with the culture channel of the organ chip, the airflow channel is used for communicating with the breathing chamber of the organ chip, and the airflow channel and the liquid chamber are suitable for communicating with an external pressure supply device.

[0007] In one possible implementation, the culture channel is at least two parallelly arranged; the liquid chamber is at least two groups corresponding to the culture channel, each group includes two liquid chambers, one of the liquid chambers in each group is used for communicating with the inlet of the culture channel, and the other liquid chamber is used for communicating with the outlet of the culture channel.

[0008] In a possible implementation, each bottom wall of the liquid chambers is provided with a liquid passing hole; the base comprises: a sealing gasket provided at the bottom of the box body, the sealing gasket being provided with a through hole in communication with the liquid passing hole; a flow channel plate provided at the side of the sealing gasket away from the box body, the flow channel plate being provided with a first connecting flow channel and a second connecting flow channel, one end of the first connecting flow channel being in communication with the liquid chamber through the through hole and the liquid passing hole in sequence, the first connecting flow channel also being in communication with the culture channel, and the second connecting flow channel being used for communication with the airflow channel; and a bracket assembly fixedly connected with the flow channel plate, the bracket assembly being used for arranging the organ chip.

[0009] In a possible implementation, the bracket assembly comprises: a fixed bracket fixed to the side of the flow channel plate away from the sealing gasket, at least one of the fixed bracket and the flow channel plate being provided with a sliding groove extending along a first direction, one end of the sliding groove along the first direction being provided with an opening; and a movable bracket used for arranging the organ chip, the movable bracket being slidingly matched with the sliding groove through the opening, and when the movable bracket is installed in place, the breathing chamber is in communication with the airflow channel through the second connecting flow channel, and the culture channel is in communication with the liquid chamber through the first connecting flow channel.

[0010] In a possible implementation, the side of the flow channel plate away from the sealing gasket is provided with a first avoiding space; the fixed bracket surrounds a second avoiding space, the second avoiding space being in communication with the first avoiding space and jointly forming an avoiding cavity, and the sliding groove is formed at the opposite two side walls of the second avoiding space along a second direction; when the movable bracket is installed in place, the organ chip is located in the avoiding cavity.

[0011] In a possible implementation, the part of the flow channel plate corresponding to the first avoiding space is provided with a plurality of first interfaces, and the plurality of first interfaces are respectively in communication with the first connecting flow channel and the second connecting flow channel; the organ chip is provided with a chip interface corresponding to each first interface, and the chip interface is adapted to be in communication with the first interface.

[0012] In a possible implementation, the breathing chambers are two, and the two breathing chambers are arranged at two sides of the culture channel respectively; the plurality of first interfaces corresponding to the second connecting flow channel are two, and each first interface is used for communication with the corresponding breathing chamber.

[0013] In a possible implementation, the movable bracket comprises a bracket bottom plate, a surrounding rib is arranged on the bracket bottom plate, the surrounding rib surrounds a placement space, and the organ chip is adapted to be arranged in the placement space; a fixing plate is arranged on one side of the surrounding rib, one end of the fixing plate is connected with the bracket bottom plate, and the other end is provided with a clamping hook, and when the movable bracket is installed in place, the clamping hook is clamped with the sealing gasket.

[0014] In a possible implementation, the orthographic projection of the box body on the base is staggered with the orthographic projection of the organ chip on the base in a first direction.

[0015] In a possible implementation, the box body comprises a box main body, and the gas flow channel and the liquid chamber are arranged in the box main body; a box cover is arranged to cover the liquid chamber and the gas flow channel, the box cover is provided with a plurality of connectors in communication with the liquid chamber and the gas flow channel respectively, and the connectors are used to communicate with an external pressure supply device.

[0016] In a possible implementation, the box cover comprises a first cover body and a second cover body arranged in layers, the connectors are formed in the first cover body, and the first cover body and the second cover body jointly define a cavity, a docking pipe is arranged on the second cover body, the docking pipe corresponds to the connectors one by one and is in communication in the cavity, and the connectors are in communication with the liquid chamber or the gas flow channel through the docking pipe.

[0017] In a possible implementation, the box cover further comprises a filter, the filter corresponds to the connectors and the docking pipes, and each filter is arranged between the corresponding connector and the docking pipe.

[0018] In another aspect, the embodiments of the present application provide an organ chip culture device, comprising the perfusion culture box.

[0019] The perfusion culture box and organ-on-a-chip culture device provided in this application embodiment are used for culturing organ-on-a-chip. The organ-on-a-chip includes a culture channel and a breathing chamber. The culture channel contains cells to be cultured. By continuously supplying culture medium into the culture channel, the flow of blood in the human body is simulated to maintain normal physiological activities of the cells. The breathing chamber is located on both sides of the culture channel. The breathing chamber contracts or expands to simulate the human breathing environment. The perfusion culture box includes a base and a box body. The liquid chamber of the box body is used to store culture medium and is connected to the culture channel. The airflow channel is connected to the breathing chamber. A pressure supply device can drive the culture medium in the liquid chamber into the culture channel, thereby realizing a continuous supply of culture medium. At the same time, the pressure device controls the contraction or expansion of the breathing chamber through the airflow channel. In this way, the liquid chamber of the box body in this application embodiment is directly connected to the culture channel. When operating, the operator only needs to install the organ-on-a-chip in the base without manually connecting the pipeline, which helps to reduce the probability of culture medium contamination and provides a cleaner culture environment for organ-on-a-chip. Attached Figure Description

[0020] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this application and, together with the description, serve to explain the principles of this application.

[0021] Figure 1 This is a schematic diagram of the perfusion culture box provided in the embodiments of this application;

[0022] Figure 2 for Figure 1 Exploded view;

[0023] Figure 3 An exploded view of the body and base of the perfusion culture box provided in the embodiments of this application;

[0024] Figure 4 A schematic diagram of the structure of the perfusion culture box provided in this embodiment of the application when the movable bracket is pulled out;

[0025] Figure 5 A schematic diagram illustrating the process of mounting an organ-on-a-chip using a perfusion culture box provided in an embodiment of this application;

[0026] Figure 6 for Figure 2 Exploded view of the middle box lid;

[0027] Figure 7 for Figure 2 A schematic diagram of the structure of a Chinese organ-on-a-chip;

[0028] Figure 8 A diagram showing the usage status of the perfusion culture box provided in the embodiments of this application in an organ-on-a-chip culture device.

[0029] Explanation of reference numerals in the attached figures:

[0030] 100 - perfusion cartridge;

[0031] 110 - base; 111 - gasket; 112 - flow channel plate; 1121 - first relief space; 1122 - first interface; 113 - bracket assembly; 1131 - fixed bracket; 1131a - second relief space; 1131b - sliding slot; 1132 - movable bracket; 1132a - bracket bottom plate; 1132b - surrounding rib; 1132c - seating space; 1132d - observation window; 1132e - fixed plate; 1132f - hook;

[0032] 120 - cartridge body; 121 - cartridge main body; 1211 - air flow channel; 1212 - liquid chamber; 1212a - liquid passing hole; 122 - cartridge cover; 1221 - first cover body; 1221a - joint; 1222 - second cover body; 1222a - counter-coupling pipe; 1223 - filter element;

[0033] 200 - organ chip;

[0034] 210 - culture channel;

[0035] 220 - respiration chamber;

[0036] 230 - chip interface;

[0037] 10 - organ chip culture device; 11 - pressure supply device; 12 - imaging device.

[0038] The specific embodiments of the application have been shown by way of example in the above figures, and will be described in more detail hereafter. These figures and this written description are not intended to limit the scope of this application in any way, but rather to illustrate various aspects of the application to those of ordinary skill in the art. DETAILED DESCRIPTION

[0039] Exemplary embodiments are described herein in detail with reference to the figures. The following description provides specific details for a particular implementation in order to provide a thorough understanding of the application. However, various implementations of the present application can be practiced without resorting to the details described in the following description. Only the

[0040] In combination with the background art, in the prior art, the culture device of the organ chip includes a culture liquid box and a chip support, the culture liquid box is used for storing culture liquid, and the chip support is used for fixing the organ chip. The organ chip is communicated with the culture liquid box through a delivery pipe, so that the culture liquid is injected into the inside of the organ chip. However, the above culture device needs to manually disassemble and assemble the delivery pipe, and the disassembly and assembly process may contaminate the delivery pipe and further contaminate the culture liquid, thereby affecting the culture environment of the organ chip.

[0041] In combination with the background art, in the prior art, the culture device of the organ chip includes a culture liquid box and a chip support, the culture liquid box is used for storing culture liquid, and the chip support is used for fixing the organ chip. The organ chip is communicated with the culture liquid box through a delivery pipe, so that the culture liquid is injected into the inside of the organ chip. However, the above culture device needs to manually disassemble and assemble the delivery pipe, and the disassembly and assembly process may contaminate the delivery pipe and further contaminate the culture liquid, thereby affecting the culture environment of the organ chip.

[0042] The technical solutions of the present application and how the technical solutions of the present application solve the above technical problems will be described in detail below with specific embodiments. The following specific embodiments can be combined with each other, and the same or similar concepts or processes may not be described again in some embodiments. The embodiments of the present application will be described below with reference to the drawings.

[0043] It should be noted that the perfusion culture box provided by the embodiments of the present application can be applied to various different organ chip culture devices.

[0044] Referring to Figure 1 , Figure 2 , Figure 7 and Figure 8 , the perfusion culture box 100 of the embodiments of the present application is used for culturing an organ chip 200. The organ chip 200 is provided with a culture channel 210 and a breathing chamber 220. The culture channel 210 has cells to be cultured therein. The culture liquid is continuously delivered in the culture channel 210 to simulate the blood flow in the human body, thereby maintaining the normal physiological activities of the cells. The breathing chamber 220 is located on both sides of the culture channel 210. The breathing chamber 220 contracts or expands to drive the shape of the culture channel 210 to change, thereby simulating the breathing environment of the human body.

[0045] The perfusion culture box 100 comprises a base 110 and a box body 120, the base 110 is suitable for arranging the organ chip 200; the box body 120 is arranged on the base 110, the box body 120 is internally provided with an airflow channel 1211 and a liquid chamber 1212, the liquid chamber 1212 is suitable for storing culture solution, the liquid chamber 1212 is used for being communicated with the culture channel 210 of the organ chip 200, the airflow channel 1211 is used for being communicated with the breathing chamber 220 of the organ chip 200, and the airflow channel 1211 and the liquid chamber 1212 are both suitable for being communicated with the external pressure supply device 11.

[0046] In the embodiment of the present application, when the organ chip 200 is cultured, the organ chip 200 only needs to be fixed in the base 110, the culture solution is injected into the liquid chamber 1212, the pressure supply device 11 is used for inflating and pressurizing the liquid chamber 1212, the culture solution is pushed into the organ chip 200, and the pressure supply device 11 continuously supplies the culture solution to the organ chip 200 by continuously applying pressure, so as to ensure that the cells maintain normal physiological activities. In this way, compared with the prior art in which the delivery pipe is connected to the organ chip 200, the liquid chamber 1212 of the perfusion culture box 100 of the embodiment of the present application is directly communicated with the culture channel 210 after the organ chip 200 is fixed, the opportunity of the organ chip 200 and the culture solution being contacted with the external environment is reduced, and thus the probability of the culture solution and the organ chip 200 being contaminated is reduced, the cleanliness of the culture environment of the organ chip 200 is ensured, and the culture quality of the cells in the organ chip 200 is improved.

[0047] Further, the airflow channel 1211 is also communicated with the breathing chamber 220, the pressure supply device 11 can pressurize or depressurize by inflating or deflating, so as to control the expansion or contraction of the breathing chamber 220 at a preset rhythm, the breathing chamber 220 is located on both sides of the airflow channel 1211, and thus the shape of the culture channel 210 changes when the breathing chamber 220 expands or contracts, so that the microenvironment of the cells is closer to the real situation in the human body, and the growth and function of the cells are facilitated.

[0048] In some implementable manners, as shown in Figure 1 、 Figure 2 、 Figure 7 and Figure 8 , the culture channel 210 of the embodiment of the present application comprises at least two parallel arranged culture channels; the liquid chamber 1212 comprises at least two groups corresponding to the culture channel 210, each group comprises two liquid chambers 1212, one liquid chamber 1212 in each group is used for being communicated with the inlet of the culture channel 210, and the other liquid chamber 1212 is used for being communicated with the outlet of the culture channel 210.

[0049] In a specific implementation, as many human tissue organs have layered structure characteristics, the culture channel 210 of the organ chip 200 is arranged to be two, which can culture different types of cells respectively, and the two culture channels 210 are connected through the intermediate membrane structure or other ways to simulate the layered tissue structure, so that the microenvironment of the cells is closer to the real situation in vivo. The culture solution required in each culture channel 210 can be the same or different, and each culture channel 210 is independent of each other, so the liquid chamber 1212 needs to be arranged as two groups corresponding to the culture channel 210.

[0050] Each group includes two liquid chambers 1212, and the two liquid chambers 1212 are respectively communicated with the inlet and outlet of one culture channel 210. In this way, the pressure supply device 11 can push the culture solution into the culture channel 210 by inflating and pressurizing the liquid chamber 1212 communicated with the inlet, and the culture solution flowing out of the culture channel 210 enters the liquid chamber 1212 communicated with the outlet. When the culture solution in the liquid chamber 1212 increases to cause the pressure to increase, the excess gas can be released through the pressure supply device 11, so as to keep the balance of the pressure in the liquid chamber 1212. In this way, new culture solution can be continuously input into the intelligent chip, and the size of the pressure adjusted by the pressure supply device 11 can also control the speed, cycle and other parameters of the culture solution flowing in the culture channel 210, which is beneficial to realize the dynamic regulation of the cell culture process, so as to simulate the dynamic changes of the organs in the human body under different physiological conditions, and is beneficial to provide a more accurate model for studying the physiological functions and pathological mechanisms of organs.

[0051] In some implementable ways, as shown in Figure 1 、 Figure 2 、 Figure 3 、 Figure 7 and Figure 8 , the bottom wall of each liquid chamber 1212 of the embodiment of the application is provided with a liquid passing hole 1212a; the base 110 includes a sealing gasket 111 and a flow channel plate 112. The sealing gasket 111 is arranged at the bottom of the box body 120, and the sealing gasket 111 is provided with a through hole communicated with the liquid passing hole 1212a; the flow channel plate 112 is arranged on the side of the sealing gasket 111 away from the box body 120, and the flow channel plate 112 is provided with a first connecting flow channel (not shown in the figure) and a second connecting flow channel (not shown in the figure). One end of the first connecting flow channel is communicated with the liquid chamber 1212 through the through hole and the liquid passing hole 1212a in sequence, and the first connecting flow channel is also communicated with the culture channel 210. The second connecting flow channel is used to be communicated with the gas flow channel 1211; the bracket assembly 113 is fixedly connected with the flow channel plate 112, and the bracket assembly 113 is used to arrange the organ chip 200.

[0052] It can be understood that the culture solution in the liquid chamber 1212 enters the culture channel 210 through the first connecting flow channel, and then is discharged through the first connecting flow channel and enters another liquid chamber 1212. The first connecting flow channel can include a first section and a second section. The two ends of the first section are respectively connected with the inlet of the culture channel 210 and the liquid passing hole 1212a of the liquid chamber 1212. The two ends of the second section are respectively connected with the outlet of the culture channel 210 and the liquid passing hole 1212a of another liquid chamber 1212. The culture solution passes through the first section, the culture channel 210 and the second section once from one liquid chamber 1212 and enters another liquid chamber 1212. After the organ chip 200 is installed on the bracket assembly 113, the inlet and outlet of the culture channel 210 of the organ chip 200 are connected with the ports of the first section and the second section, so that the step of manually connecting the delivery pipe is reduced, the possibility of the culture solution and the organ chip 200 contacting the external environment is reduced, and the probability of the culture solution being contaminated is reduced, thereby being beneficial to protecting the clean and sterile culture environment inside the organ chip 200.

[0053] It should be noted that the diameter of the first connecting flow channel is small. When the organ chip 200 is installed, a drop of culture solution can be dropped at the inlet and outlet of the culture channel 210, and a drop of culture solution is also reserved at the ports of the first section and the second section. When the inlet and the outlet are opposite to the ports of the first section and the second section respectively, the culture solution can enter the culture channel 210 by means of the surface tension of the liquid, so as to ensure that the first connecting flow channel is connected with the culture channel 210 of the organ chip 200.

[0054] In addition, the sealing pad 111 arranged between the bottom of the box body 120 and the flow channel plate 112 can prevent the culture solution from overflowing from the liquid passing hole 1212a and contaminating the perfusion culture box 100, and can also improve the sealing performance of the perfusion culture box 100, avoid external impurities such as dust from entering the inside to contaminate the culture solution, and reduce the probability of the culture solution being contaminated.

[0055] Further, the airflow channel 1211 is connected with the breathing chamber 220 through the second connecting channel. The air suction or inflation of the pressure device can cause the air pressure in the breathing chamber 220 to decrease or increase, so as to control the contraction or expansion of the breathing chamber 220, and drive the shape of the culture channel 210 beside the breathing chamber 220 to change, so that the culture environment of the cells is more consistent with the real situation in the human body.

[0056] In some possible implementation manners, referring to Figures 1 to 8As shown, the bracket assembly 113 of the embodiment of the present application comprises: a fixed bracket 1131 fixed to one side of the flow channel plate 112 away from the sealing gasket 111, and at least one of the fixed bracket 1131 and the flow channel plate 112 is provided with a sliding groove 1131b extending along the first direction, and one end of the sliding groove 1131b along the first direction has an opening; and a movable bracket 1132 for arranging the organ chip 200, the movable bracket 1132 is slidingly matched with the sliding groove 1131b through the opening, and when the movable bracket 1132 is installed in place, the breathing chamber 220 is communicated with the airflow channel 1211 through the second connecting flow channel, and the culture channel 210 is communicated with the liquid chamber 1212 through the first connecting flow channel. Figure 1 The X direction is the first direction, and the Y direction is the second direction.

[0057] In the specific implementation, first, the movable bracket 1132 is pulled out, the organ chip 200 is fixed on the movable bracket 1132, and then the movable bracket 1132 is pushed along the sliding groove 1131b, and when the movable bracket 1132 is pushed to the end of the sliding groove 1131b, the culture channel 210 is communicated with the liquid chamber 1212 through the first connecting flow channel. The operation is convenient, and the position of the movable bracket 1132 can be limited through the sliding groove 1131b to ensure that the inlet and outlet of the culture channel 210 of the organ chip 200 and the outlet of the breathing chamber 220 are opposite to the ports of the first connecting flow channel and the second connecting flow channel respectively, the sliding groove 1131b provides convenience for the installation and fixation of the movable bracket 1132, so that the structure of the whole device is more compact and reasonable, the operation convenience and accuracy are improved, the installation accuracy of the organ chip 200 is facilitated to be ensured, and the contact of the hands of the experimental personnel with the organ chip 200 and the culture solution is reduced, so that the possibility of contamination of the culture solution is further reduced.

[0058] In some implementable manners, referring to Figures 1 to 8 As shown, the flow channel plate 112 away from the sealing gasket 111 is provided with a first avoiding space 1121; the fixed bracket 1131 surrounds a second avoiding space 1131a, the second avoiding space 1131a is communicated with the first avoiding space 1121 and forms an avoiding cavity together, and the sliding groove 1131b is formed on the opposite two side walls of the second avoiding space 1131a along the second direction; and when the movable bracket 1132 is installed in place, the organ chip 200 is in the avoiding cavity.

[0059] It can be understood that the organ chip 200 is located in the installation cavity, the flow channel plate 112 and the fixed bracket 1131 can provide good protection and stable support for the organ chip 200, and the existence of the avoiding cavity provides sufficient space for the installation and operation of the organ chip 200, avoids damage to the organ chip 200 in the installation process, and ensures the stability and reliability of the organ chip 200 in the use process.

[0060] In some possible implementation manners, referring to Figure 1 、 Figure 2 、 Figure 3 、 Figure 7 and Figure 8 , the flow channel plate 112 is provided with a plurality of first interfaces 1122 corresponding to the first avoiding space 1121, and the plurality of first interfaces 1122 are respectively in communication with the first connection flow channel and the second connection flow channel; and the organ chip 200 is provided with a chip interface 230 corresponding to the first interface 1122, and the chip interface 230 is adapted to be in communication with the first interface 1122.

[0061] In a specific implementation, the communication between the chip interface 230 and the first interface 1122 forms a complete fluid passage between the first connection flow channel and the culture channel 210. In this way, the culture solution can flow smoothly between the culture channel 210 and the flow channel plate 112, providing stable nutrient supply and metabolic waste discharge passage for the cells in the organ chip 200, ensuring that the cells can be in a good physiological state during the culture process, thereby improving the culture effect of the organ chip 200 and the accuracy of the experiment.

[0062] Meanwhile, the airflow channel 1211 is also in communication with the breathing chamber 220 through the first interface 1122 and the chip interface 230, thereby ensuring that the pressure supply device 11 can control the contraction or expansion of the breathing chamber 220.

[0063] In some possible implementation manners, referring to Figure 1 、 Figure 2 、 Figure 3 、 Figure 7 and Figure 8 , the two breathing chambers 220 are respectively arranged on the two sides of the culture channel 210; and the plurality of first interfaces 1122 corresponding to the second connection flow channel are two, and each first interface 1122 is used for being in communication with a corresponding breathing chamber 220.

[0064] It can be understood that the two breathing chambers 220 are respectively located on the two sides of the culture channel 210, and when the breathing chambers 220 contract or expand, the culture channel 210 can be stretched or extruded from the two sides of the culture channel 210, thereby controlling the shape of the culture channel 210 to change at a preset frequency. In order to ensure that the contraction frequencies of the two breathing chambers 220 remain consistent, the two breathing chambers 220 are simultaneously in communication with the airflow channel 1211 through the first interface 1122, so that when the pressure supply device 11 performs air suction and exhaust, the two breathing chambers 220 can be ensured to contract or expand synchronously, thereby ensuring that the culture channel 210 is subjected to the same force on the two sides, guaranteeing the symmetry of the deformation of the culture channel 210, and being beneficial to further improving the culture effect of the organ chip 200 and the accuracy of the experiment.

[0065] In some possible implementation manners, referring to Figure 1 , Figure 2 , Figure 3 , Figure 7 and Figure 8 , the movable bracket 1132 of the embodiment of the present application comprises a bracket bottom plate 1132a and a fixing plate 1132e, the bracket bottom plate 1132a is provided with a surrounding rib 1132b, the surrounding rib 1132b surrounds a placement space 1132c, and the organ chip 200 is adapted to be arranged in the placement space 1132c; the fixing plate 1132e is arranged on one side of the surrounding rib 1132b, one end of the fixing plate 1132e is connected with the bracket bottom plate 1132a, and the other end is provided with a clamping hook 1132f. When the movable bracket 1132 is installed in place, the clamping hook 1132f is clamped with the sealing gasket 111.

[0066] Specifically, the bracket bottom plate 1132a provides a stable support platform for the organ chip 200, and the surrounding rib 1132b is beneficial to ensure that the organ chip 200 does not shift or shake during operation. When the movable bracket 1132 is installed in place, the clamping hook 1132f can be tightly clamped with the sealing gasket 111 to form a reliable fixing structure, which is beneficial to ensure the stability and safety of the organ chip 200 in the placement space 1132c, and also facilitates the installation and disassembly of the movable bracket 1132, thereby improving the convenience and efficiency of operation. In addition, the clamping of the clamping hook 1132f with the sealing gasket 111 is also beneficial to enhance the sealing of the entire device and prevent the culture solution from leaking.

[0067] In specific implementation, as shown in Figure 5 , the movable bracket 1132 can be first slid along the first direction and then rotated along the direction indicated by the arrow in the figure, so as to fix the movable bracket 1132 on the fixed bracket 1131, and the operation is convenient.

[0068] In some possible implementation manners, referring to Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 7 and Figure 8 , the orthographic projection of the box body 120 on the base 110 is staggered with the orthographic projection of the organ chip 200 on the base 110 along the first direction.

[0069] In specific implementation, the box body 120 and the organ chip 200 are staggered, which can avoid interference between the box body 120 and the organ chip 200, and facilitate the experimental personnel to observe the state of the organ chip 200 in real time, and the box body 120 blocks the observation field of view.

[0070] Further, an observation window 1132d corresponding to the position of the culture channel 210 can be formed on the tray bottom plate 1132a. Through the observation window 1132d, the state of the cells in the organ chip 200 can be monitored in real time, which facilitates the experimental personnel to monitor the experimental progress in real time, discover potential problems in time, and adjust the experimental conditions. At the same time, the observation window 1132d can also be used in cooperation with the imaging device 12 and other detection equipment. The experimental personnel can use the imaging device 12 and other equipment to observe and analyze the cells in the organ chip 200 at high magnification and high precision, and obtain more detailed information about the structure and function of the cells, thereby providing support for in-depth scientific research.

[0071] In some implementable manners, as shown in Figure 1 , Figure 2 , Figure 6 , Figure 7 and Figure 8 , the box body 120 of the embodiment of the present application comprises: a box main body 121 and a box cover 122, the airflow channel 1211 and the liquid chamber 1212 are both formed in the box main body 121; the box cover 122, the box cover 122 is used to cover the liquid chamber 1212 and the airflow channel 1211, and the box cover 122 is provided with a plurality of connectors 1221a in communication with the liquid chamber 1212 and the airflow channel 1211, respectively, and the connectors 1221a are used to communicate with the external pressure supply device 11.

[0072] It can be understood that the box cover 122 can prevent dust and other impurities from the outside from entering the liquid chamber 1212, thereby reducing the possibility of contamination of the culture solution, and the liquid chamber 1212 and the airflow channel 1211 are only connected to the external pressure supply device 11 through the connectors 1221a, which is conducive to ensuring that the air pressure in the liquid chamber 1212 or the airflow channel 1211 changes in time when the pressure supply device 11 is inflated or deflated, thereby driving the flow of the culture solution or the contraction and expansion of the breathing chamber 220.

[0073] In some implementable manners, as shown in Figure 1 , Figure 2 , Figure 6 , Figure 7 and Figure 8 , the box cover 122 of the embodiment of the present application comprises: a first cover body 1221 and a second cover body 1222 arranged in layers, the connectors 1221a are all formed in the first cover body 1221, the first cover body 1221 and the second cover body 1222 jointly define a cavity, the second cover body 1222 is provided with a docking pipe 1222a, the docking pipe 1222a corresponds to the connectors 1221a one by one and communicates in the cavity, and the connectors 1221a communicate with the liquid chamber 1212 or the airflow channel 1211 through the docking pipe 1222a.

[0074] The first cover 1221 can be made of a material with high hardness, such as plastic, to ensure the structural strength of the box cover 122. The second cover 1222 can be made of a material with good sealing performance, such as rubber or silica gel, to improve the sealing performance of the box body 120 and prevent the culture solution from being contaminated. Of course, the structures of the first cover 1221 and the second cover 1222 are not limited in the embodiments of the present application, and can be reasonably selected according to actual needs.

[0075] Meanwhile, the communication between the connecting pipe 1222a and the connector 1221a is conducive to preventing air leakage and ensuring that the pressure supply device 11 accurately controls the flow rate of the culture solution and the frequency of the expansion and contraction of the breathing chamber 220, thereby improving the accuracy of the experiment.

[0076] In some implementable manners, as shown in Figure 1 , Figure 2 , Figure 6 , Figure 7 and Figure 8 , the box cover 122 of the embodiment of the present application further includes: a plurality of filter pieces 1223 corresponding to the connectors 1221a and the connecting pipes 1222a, and each filter piece 1223 is arranged between a corresponding connector 1221a and connecting pipe 1222a.

[0077] In specific implementation, the filter piece 1223 can prevent dust and other impurities in the gas from entering the liquid chamber 1212 through the connecting pipe 1222a, thereby ensuring that the culture solution is not contaminated and that the cells in the organ chip 200 grow in a clean and sterile environment.

[0078] As shown in Figure 1 , Figure 2 and Figure 8 , the embodiment of the present application further provides an organ chip culture device 10, which includes any of the perfusion culture boxes 100 described above.

[0079] The structure and working principle of the perfusion culture box 100 are described in detail in the above embodiments, and will not be repeated here.

[0080] In the embodiment of the present application, the organ chip culture device 10 can further include a pressure supply device 11 and an imaging device 12. The pressure supply device 11 communicates with the perfusion culture box 100, and the imaging device 12 is arranged below the perfusion culture box 100 and is used to observe the state of the cells in the organ chip 200 in real time through the observation window 1132d. The imaging device 12 can be an optical microscope, an electron microscope, etc. The structure of the pressure supply device 11 is also various, and is known to those skilled in the art. The pressure supply device 11 can include a gas cylinder, a connecting pipeline, a proportional valve, a pressure gauge, a gas pump, etc., and is not limited in the embodiment of the present application.

[0081] In conclusion, the perfusion culture box 100 provided by the embodiment of the present application can fix the organ chip 200 on the movable base plate, then slide the movable base plate along the sliding groove 1131b on the fixed bracket 1131 to the end of the sliding groove 1131b, and then rotate the movable base plate to make the clamping hook 1132f on the fixed plate 1132e clamped with the fixed bracket 1131, so that the culture channel 210 of the organ chip 200 is communicated with the liquid chamber 1212 through the first connecting flow channel on the flow channel plate 112, the culture solution is perfused in the liquid chamber 1212, and the culture solution can be continuously supplied into the culture channel 210 by driving the pressure supply device 11. Compared with the culture solution delivered through the delivery pipe, the perfusion culture box 100 of the embodiment of the present application reduces the opportunity of direct contact of the culture solution and the organ chip 200 with the external environment, thereby reducing the possibility of contamination of the culture solution and the organ chip 200, and is beneficial to guarantee that the culture environment of the cells in the organ chip 200 meets the experimental requirements and improves the accuracy of experimental data.

[0082] In the description of the embodiments of the present application, it should be noted that, unless otherwise explicitly specified and limited, the terms "mount", "connect", "connection" should be understood in a broad sense, for example, can be fixedly connected, can be indirectly connected through an intermediate medium, can be the communication inside two elements or the interaction relationship between two elements. For those skilled in the art, the specific meaning of the above terms in the embodiments of the present application can be understood according to the specific circumstances.

[0083] In the embodiments of the present application or the devices or elements implied by the embodiments of the present application must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation of the embodiments of the present application. In the description of the embodiments of the present application, the meaning of "a plurality of" is two or more, unless otherwise specified and limited.

[0084] The terms "first", "second", "third", "fourth" and the like (if any) in the description of the embodiments of the present application and the above drawings are used to distinguish similar objects, and do not necessarily have to describe a specific order or sequence. It should be understood that the data thus used can be interchanged under appropriate circumstances, so that the embodiments of the present application described herein can be implemented in an order other than those illustrated or described herein.

[0085] In addition, the terms "include" and "have" and any variations thereof are intended to cover non-exclusive inclusion, for example, a process, method, system, product or device including a series of steps or units does not have to be limited to those steps or units clearly listed, but can include other steps or units not clearly listed or inherent to these processes, methods, products or devices.

[0086] The term "multiple" in the present text refers to two or more. The term "and / or" in the present text only describes the association relationship of the associated objects, which means that there can be three relationships, for example, A and / or B can represent the three cases of A existing alone, A and B existing together, and B existing alone.

[0087] It can be understood that various numerical numbers involved in the embodiments of the present application are only distinguished for convenience of description, and are not used to limit the scope of the embodiments of the present application.

[0088] It can be understood that the size of the serial number of each process in the embodiments of the present application does not mean the order of execution, and the execution order of each process should be determined according to its function and inherent logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0089] Other embodiments of the application will be apparent to those skilled in the art from consideration of the specification and practice of the application disclosed herein. It is intended that the specification and examples be considered as exemplary only, with the true scope and spirit of the application being indicated by the following claims.

[0090] It should be understood that the present application is not limited to the precise construction that has been described above and shown in the accompanying drawings, and that various modifications and changes can be made by those skilled in the art without departing from the scope of the present application. The scope of the present application is only limited by the appended claims.

Claims

1. A perfusion culture chamber (100) for culturing organ-on-a-chip (200), wherein the organ-on-a-chip (200) is provided with a culture channel (210) and a respiration chamber (220), characterized in that, The perfusion culture box (100) includes: A base (110) adapted to hold the organ chip (200); A housing (120) is disposed on the base (110). The housing (120) is provided with an airflow channel (1211) and a liquid chamber (1212). The liquid chamber (1212) is suitable for storing culture medium. The liquid chamber (1212) is used to communicate with the culture channel (210) of the organ-on-a-chip (200). The airflow channel (1211) is used to communicate with the breathing chamber (220) of the organ-on-a-chip (200). Both the airflow channel (1211) and the liquid chamber (1212) are suitable for communicating with an external pressure supply device (11).

2. The perfusion culture box (100) according to claim 1, characterized in that, The culture channels (210) are at least two arranged in parallel; The liquid chambers (1212) are at least two groups corresponding to the culture channel (210), each group including two liquid chambers (1212), one of the liquid chambers (1212) in each group is used to communicate with the inlet of the culture channel (210), and the other liquid chamber (1212) is used to communicate with the outlet of the culture channel (210).

3. The perfusion culture box (100) according to claim 2, characterized in that, Each of the liquid chambers (1212) has a liquid passage hole (1212a) on its bottom wall; The base (110) includes: A sealing gasket (111) is provided at the bottom of the box body (120), and the sealing gasket (111) is provided with a through hole that communicates with the liquid passage hole (1212a); A flow channel plate (112) is disposed on the side of the sealing gasket (111) facing away from the box body (120). The flow channel plate (112) is provided with a first connecting flow channel and a second connecting flow channel. One end of the first connecting flow channel is connected to the liquid chamber (1212) in sequence through the through hole and the liquid passage hole (1212a). The first connecting flow channel is also connected to the culture channel (210). The second connecting flow channel is used to connect to the airflow channel (1211). A bracket assembly (113) is fixedly connected to the flow channel plate (112), and the bracket assembly (113) is used to set the organ-on-a-chip (200).

4. The perfusion culture box (100) according to claim 3, characterized in that, The bracket assembly (113) includes: A fixed bracket (1131) is fixed to the side of the flow channel plate (112) facing away from the sealing gasket (111). At least one of the fixed bracket (1131) and the flow channel plate (112) is provided with a groove (1131b) extending in a first direction. One end of the groove (1131b) in the first direction has an opening. A movable bracket (1132) is used to set the organ-on-a-chip (200). The movable bracket (1132) is slidably engaged with the slide groove (1131b) via the opening. When the movable bracket (1132) is installed in place, the breathing chamber (220) is connected to the airflow channel (1211) through the second connecting channel, and the culture channel (210) is connected to the liquid chamber (1212) through the first connecting channel.

5. The perfusion culture box (100) according to claim 4, characterized in that, The flow channel plate (112) has a first clearance space (1121) on the side opposite to the sealing gasket (111); The fixed bracket (1131) encloses a second clearance space (1131a), which is connected to the first clearance space (1121) and together forms a clearance cavity. The slide groove (1131b) is formed on the opposite side walls of the second clearance space (1131a) along the second direction. When the movable bracket (1132) is installed in place, the organ-on-a-chip (200) is located in the clearance cavity.

6. The perfusion culture box (100) according to claim 5, characterized in that, The flow channel plate (112) is provided with a plurality of first interfaces (1122) at the part corresponding to the first clearance space (1121), and the plurality of first interfaces (1122) are respectively connected to the first connecting flow channel and the second connecting flow channel; The organ chip (200) is provided with a chip interface (230) that corresponds one-to-one with the first interface (1122), and the chip interface (230) is adapted to communicate with the first interface (1122).

7. The perfusion culture box (100) according to claim 6, characterized in that, There are two breathing chambers (220), and the two breathing chambers (220) are respectively located on both sides of the culture channel (210); The plurality of first interfaces (1122) corresponding to the second connecting channel are two in number, and each first interface (1122) is used to communicate with the corresponding breathing chamber (220).

8. The perfusion culture box (100) according to claim 4, characterized in that, The movable bracket (1132) includes: The bracket base plate (1132a) is provided with a surrounding rib (1132b), the surrounding rib (1132b) enclosing a placement space (1132c), and the organ chip (200) is adapted to be placed in the placement space (1132c); A fixing plate (1132e) is provided on one side of the surrounding rib (1132b). One end of the fixing plate (1132e) is connected to the bracket base plate (1132a), and the other end is provided with a hook (1132f). When the movable bracket (1132) is installed in place, the hook (1132f) engages with the sealing gasket (111).

9. The perfusion culture box (100) according to any one of claims 1-8, characterized in that, The orthographic projection of the housing (120) on the base (110) and the orthographic projection of the organ chip (200) on the base (110) are offset along a first direction.

10. The perfusion culture box (100) according to any one of claims 1-8, characterized in that, The housing (120) includes: The box body (121) has the airflow channel (1211) and the liquid chamber (1212) both located in the box body (121); A cover (122) is provided to cover the liquid chamber (1212) and the airflow channel (1211). The cover (122) is provided with a plurality of connectors (1221a) that are respectively connected to the liquid chamber (1212) and the airflow channel (1211). The connectors (1221a) are used to connect to an external pressure supply device (11).

11. The perfusion culture box (100) according to claim 10, characterized in that, The lid (122) includes a first lid body (1221) and a second lid body (1222) arranged in layers. The connectors (1221a) are all formed on the first lid body (1221). The first lid body (1221) and the second lid body (1222) together define a cavity. The second lid body (1222) is provided with a connecting pipe (1222a). The connecting pipe (1222a) corresponds one-to-one with the connector (1221a) and communicates with it in the cavity. The connector (1221a) communicates with the liquid chamber (1212) or the airflow channel (1211) through the connecting pipe (1222a).

12. The perfusion culture box (100) according to claim 11, characterized in that, The cover (122) further includes a filter element (1223), which is a plurality of filters corresponding to the connector (1221a) and the connecting pipe (1222a), and each filter element (1223) is disposed between the corresponding connector (1221a) and the connecting pipe (1222a).

13. An organ-on-a-chip culture device 10, characterized in that, Includes the perfusion culture box (100) according to any one of claims 1-12.

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