A gas distribution assembly, a gas distribution structure, a cell culture device and a culture apparatus

Abstract

The application relates to the technical field of organ chip, and provides a gas distribution assembly, a gas distribution structure, a cell culture device and a culture equipment.The gas distribution assembly comprises a ventilation matrix and a control valve, a plurality of passages are formed in the ventilation matrix, the control valve is connected to the ventilation matrix, the control valve is connected to at least part of the passages of the plurality of passages, and the control valve is used for controlling the opening and closing of the passages. The embodiment of the application can individually control ventilation of each organ chip.

Description

Technical Field

[0001] This application relates to the field of organ-on-a-chip technology, and in particular to a gas distribution component, gas distribution structure, cell culture device and culture equipment. Background Technology

[0002] Organ-on-a-chip plays an important role in verifying the response of drugs to human organs. Because organ-on-a-chip can differentiate cells into cell types with organoid characteristics, it can more accurately simulate the physiological structure and function of human organs than conventional preclinical models (two-dimensional cell models, three-dimensional spherical cell models, and various experimental animal models). Organ-on-a-chip has gradually replaced conventional preclinical models in drug research and other applications.

[0003] To inject culture medium into organ-on-a-chip, the culture equipment used for organ-on-a-chip typically uses gas pressure to force the culture medium into the organ-on-a-chip. When multiple organ-on-a-chips need to be injected with culture medium, the gas pressure generated by the culture equipment is difficult to control individually for each organ-on-a-chip, and it is impossible to control the on / off and flow of culture medium for each organ-on-a-chip. Utility Model Content

[0004] This application provides a gas distribution component, a gas distribution structure, a cell culture device, and a culture equipment, which can individually control the ventilation of each organ-on-a-chip.

[0005] The first aspect of this application provides a gas distribution assembly, comprising:

[0006] A ventilated substrate, wherein multiple passages are formed inside the ventilated substrate;

[0007] And a control valve, the control valve being connected to the venting body and being connected to at least a portion of the plurality of said passages, for controlling the opening and closing of a portion of said passages.

[0008] According to the gas distribution component described in the first aspect of this application, the gas distribution component is a combination structure of a control valve and a ventilation substrate. Through the interventional control of the passage by the control valve, the on / off control and flow control of different passages can be realized, so that the ventilation substrate can selectively connect to different culture boxes / organ-on-a-chips, thereby realizing individual control of ventilation for each culture box / organ-on-a-chip, thereby realizing the on / off control and flow control of culture medium for each culture box / organ-on-a-chip, which can improve the culture effect of organ-on-a-chips.

[0009] In one possible implementation, the ventilation substrate includes at least one main passage and multiple sets of branch passages, each set of branch passages being connected to the main passage, and the control valve being connected to one of the branch passages.

[0010] In one possible implementation, the ventilated substrate has a plurality of ventilated inlets at one end along its length and a plurality of ventilated outlets at the other end along its length, and the main passage connects the ventilated inlets and the ventilated outlets.

[0011] In one possible implementation, the side of the ventilated substrate is provided with a plurality of branch outlets, the branch channels connecting the branch outlets to the main channel.

[0012] In one possible implementation, the ventilated substrate has multiple ventilated inlets at one end along its length, and the other end along its length is a closed end, with the main passage extending from the ventilated inlets to the closed end.

[0013] In one possible implementation, each set of branch passages includes multiple branch passages, and the control valves are provided for each set of branch passages, with the number of control valves being the same as the number of branch passages.

[0014] In one possible implementation, the control valve includes a solenoid valve.

[0015] A second aspect of this application provides a gas distribution structure, comprising:

[0016] Driver components;

[0017] And a gas distribution component, wherein the driving component is used to drive the gas distribution component to move along the output direction of the driving component.

[0018] According to the gas distribution structure described in the second aspect of this application, in addition to the functions of the gas distribution component, the driving component can drive the gas distribution component to move, so as to facilitate the gas distribution component to form a connection with the organ-on-a-chip.

[0019] A third aspect of this application provides a cell culture apparatus, comprising:

[0020] Culture box structures, including organ-on-a-chip;

[0021] And a gas distribution structure, wherein the gas distribution component in the gas distribution structure can be connected to or disconnected from the organ-on-a-chip.

[0022] A fourth aspect of this application provides a culture device, including the cell culture apparatus described above. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 A schematic diagram of a culture device provided according to an embodiment of this application is shown;

[0025] Figure 2 This shows a structural schematic diagram of a culture device provided according to an embodiment of this application from another angle;

[0026] Figure 3 A schematic diagram of a top plate according to an embodiment of this application is shown;

[0027] Figure 4 A schematic diagram of a cell culture apparatus provided according to an embodiment of this application is shown;

[0028] Figure 5 A schematic diagram of another cell culture apparatus provided according to an embodiment of this application is shown;

[0029] Figure 6 A schematic diagram of a culture box structure provided according to an embodiment of this application is shown;

[0030] Figure 7 A schematic diagram of a culture box provided according to an embodiment of this application is shown;

[0031] Figure 8 An exploded view of a culture box provided according to an embodiment of this application is shown;

[0032] Figure 9 A schematic diagram of a lifting drive assembly according to an embodiment of this application is shown;

[0033] Figure 10 This shows a structural schematic diagram of a lifting drive assembly provided according to an embodiment of this application from another angle;

[0034] Figure 11 A schematic diagram of the structure of a ventilated substrate provided according to an embodiment of this application is shown;

[0035] Figure 12 A perspective view of a ventilated substrate provided according to an embodiment of this application is shown.

[0036] Figure label:

[0037] 10-Cell culture apparatus;

[0038] 11-Cultivation box structure; 111-Tray; 112-Cultivation box; 113-Organ-on-a-chip; 1111-Mounting position; 1112-Force application part; 1113-Irregular structure; 112a-Cavity; 1121-Box body; 1122-Box lid; 1123-Divider; 1121a-Mounting groove; 1122a-Air pressure interface;

[0039] 12-Gas distribution structure; 121-Lifting drive assembly; 122-Gas distribution assembly; 123-Guide assembly; 124-Force-bearing component; 1211-Drive motor; 1212-Transmission assembly; 1213-Pushing component; 1214-Drive base; 1215-Displacement monitoring assembly; 1221-Ventilation base; 1222-Control valve; 1231-Guide rod; 1232-Guide block; 1233-Reset component; 1212a-Drive shaft; 1212b- Transmission protrusion; 1213a-Force-bearing platform; 1214a-Moving cavity; 1214b-First mounting part; 1214c-Second mounting part; 1214d-Third mounting part; 1221a-Main passage; 1221b-Branch passage; 1221c-Ventilation inlet; 1221d-Ventilation outlet; 1221e-Branch outlet; 1214b1-Plate body; 1214c1-Receiving cavity; 1214c2-Side plate; 1214d1-Mounting hole;

[0040] 13-Base; 131-Substrate; 132-Support frame; 133-Mounting plate; 1311-Window; 1312-Groove;

[0041] 20 - Imaging device;

[0042] 21-Base; 21a-Mounting cavity; 211-Base plate; 212-Support column; 213-Top plate; 2131-Shooting port; 2132-Slot;

[0043] 22-Imaging mechanism; 221-Imaging drive assembly; 222-Camera assembly. Detailed Implementation

[0044] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0045] In recent years, with the development of science and technology, organoid and organ-on-a-chip culture technologies have enabled cells to differentiate into cell types with organoid characteristics. Through organoid culture technology, the cell types formed in the culture medium can have similar spatial organization and some functions of the corresponding organs. Organ-on-a-chip can more realistically simulate the physiological structure and function of human organs than conventional preclinical models (two-dimensional cell models, three-dimensional spherical cell models, and various experimental animal models, etc.). Organ-on-a-chip has gradually replaced conventional preclinical models in applications such as drug research.

[0046] To enable cells to be cultured in an organ-on-a-chip and gradually form organs that represent the corresponding physiological structures and functions, specialized culture equipment is typically required. This equipment usually provides a specific carbon dioxide environment suitable for cell culture, as well as the necessary growth conditions, including appropriate temperature and humidity. By placing the organ-on-a-chip in the equipment and culturing it for a period of time, the cell type corresponding to the organ can be obtained.

[0047] Organ-on-a-chip (OAS) typically requires initial placement into a culture cassette to form the cassette structure before being loaded into a culture device. The culture device then positions the OAS indirectly by positioning the culture structure. Compared to the OAS itself, the culture cassette structure has peripheral structures that facilitate easier positioning, allowing for more precise clamping and placement of the OAS into the culture device. The culture cassette structure can include multiple cassettes, each corresponding to one OAS, enabling the culture of multiple OAS within a single culture cycle, thus achieving highly efficient OAS culture.

[0048] In addition to the above, to culture and obtain the desired cell types, the culture medium needs to be injected into the organ-on-a-chip. For this purpose, the culture equipment needs to be equipped with a gas supply device that can introduce gas into the organ-on-a-chip, or the gas supply device can first introduce gas into the culture chamber and then allow the gas to enter the organ-on-a-chip. The working principle of the above two methods is to use air pressure to force the culture medium into the organ-on-a-chip. In the above-mentioned equipment with multiple culture chambers, when multiple organ-on-a-chips need to be injected with culture medium, the air pressure generated by the culture equipment is difficult to control individually for each organ-on-a-chip, and the flow rate and on / off control of the culture medium cannot be performed for each organ-on-a-chip, which will affect the culture effect of the culture equipment on the organ-on-a-chip.

[0049] On the other hand, before the gas generated by the gas supply device enters the organ-on-a-chip, the relevant tubing of the gas supply device needs to be connected to the organ-on-a-chip or culture chamber. Currently, the common method is to manually hold the relevant tubing to connect the tubing to the organ-on-a-chip, which is cumbersome and can easily affect the culture environment, thus introducing the risk of contamination. Some culture devices are also equipped with related devices that can drive the movement of relevant mechanisms and connect the tubing in these mechanisms to the organ-on-a-chip, but these mechanisms generally have a complex structure, making the overall structure of the culture device tend to be complex, and the presence of these mechanisms is not conducive to the arrangement of various tubing.

[0050] Based on the aforementioned situation and problems, this application provides a gas distribution structure that connects a gas supply device and an organ-on-a-chip. This gas distribution structure can, to a certain extent, replace tubing. Gas generated in the gas supply device can enter the organ-on-a-chip via this gas distribution structure. Simultaneously, the gas distribution structure is configured to move at least partially in a straight line, moving closer to or further away from the organ-on-a-chip, thereby achieving connection and separation between the gas distribution structure and the organ-on-a-chip. Using linear motion reduces the requirements on the mechanism, and since the gas distribution structure can act as part of the tubing, the structure of the culture equipment can be simplified.

[0051] On the other hand, based on the fact that the gas distribution structure can act as a partial pipeline, the embodiments of this application also make detailed designs for the gas distribution structure. These designs mainly include forming passages inside the gas distribution structure. It can be understood that the main structural part of the gas distribution structure is a solid structure, and the passages can be formed inside the gas distribution structure. The passages can lead to each organ-on-a-chip, and these passages can be used as pipelines. Compared with traditional pipelines, the solid part of the gas distribution structure is larger. Therefore, other solid structures can be set on the gas distribution structure. These solid structures can be, for example, structures that can individually control the opening and closing of the passages. The layered matching and interaction of these solid structures can realize the individual control of the ventilation of each organ-on-a-chip, thereby realizing the opening and closing of the culture medium and the flow control of each organ-on-a-chip, which can improve the culture effect of the organ-on-a-chip.

[0052] As can be seen from the following embodiments, the embodiments of this application mainly introduce the functional branches of cell culture in the culture equipment. The following description does not delve into the specific structures of devices such as culture boxes and organ-on-a-chip, or the combined structures of culture boxes and organ-on-a-chip. More specific structures of culture boxes and organ-on-a-chip can be understood by referring to related technologies. The following embodiments of this application mainly focus on the gas distribution structure for detailed description. The content regarding the functional branches of cell culture can be included in the overall scope of the cell culture device; that is, the culture box structure, gas distribution structure, etc., in the embodiments of this application can all be considered part of the cell culture device.

[0053] In addition, as a culture device, in order to monitor the state of the cell culture process in real time, the culture device can also be equipped with an imaging device, which is equipped with at least a camera lens. The camera lens can observe the culture state of the cells through necessary windows. These windows can be designed in places that are conducive to the observation of the camera lens, for example, the windows can be designed at the bottom of the cell culture device.

[0054] Therefore, the culture device in this application embodiment mainly includes a cell culture device, an imaging device, and the aforementioned gas supply device. The cell culture device is mainly used to complete the culture of cells, the imaging device is mainly used to monitor the culture status of cells in real time, and the gas supply device is used to introduce gas into the organ-on-a-chip or culture box in the cell culture device so that the culture medium can enter the organ-on-a-chip.

[0055] The embodiments of this application will now be described in further detail with reference to the accompanying drawings.

[0056] Figure 1 A schematic diagram of a culture device provided according to an embodiment of this application is shown; Figure 2 This shows a structural schematic diagram of a culture device provided according to an embodiment of this application from another angle; Figure 3 A schematic diagram of the structure of a top plate 213 provided according to an embodiment of this application is shown.

[0057] In the embodiments of this application, please refer to Figure 1 The culture equipment includes a cell culture device 10 arranged vertically and an imaging device 20, wherein... Figure 1 In the example shown, the cell culture device 10 is located above the imaging device 20, and the cell culture device 10 may be mounted on the imaging device 20.

[0058] The vertical arrangement of the cell culture device 10 and the imaging device 20 gives the culture equipment a vertical structure. The cell culture device 10 can be located higher than the imaging device 20. In other words, the cell culture device 10 can be located in a suspended environment, which is more conducive to cell culture.

[0059] In the embodiments of this application, please refer to Figure 1 and Figure 2 The imaging device 20 includes a base 21 and an imaging mechanism 22. The base 21 has a mounting cavity 21a, and the imaging mechanism 22 is installed in the mounting cavity 21a.

[0060] The base 21 can have an open structure on all four sides. For example, in some embodiments, the base 21 may include a base plate 211, support columns 212, and a top plate 213. The base plate 211 and the top plate 213 can be flat and parallel to each other. The support columns 212 connect the base plate 211 and the top plate 213. The number of support columns 212 can be set according to actual needs. For example, in... Figure 1 and Figure 2 In the example shown, there are 4 support columns 212. It is understood that in other embodiments, the number of support columns 212 may vary, for example, there may be 6 or 8 support columns 212.

[0061] The base plate 211 primarily serves as a support structure for the imaging mechanism 22, which can be mounted on it. The specific form of the base plate 211 is not limited; for example, in... Figure 1 In the example shown, the base plate 211 has a cuboid structure. To maintain the structural adaptability of the base 21, the top plate 213 can also be a cuboid structure. The support columns 212 can be set at the edge of the base plate 211. Preferably, when using four support columns 212, the four support columns 212 can be set at the corners of the base plate 211, which provides more space for the installation of the imaging mechanism 22.

[0062] In some embodiments, the support column 212 can be designed as a telescopic structure, such as an electric push rod or similar structure, so that the distance between the top plate 213 and the bottom plate 211 can be changed. This allows for easy adjustment of the height of the cell culture device 10 and the installation space of the imaging mechanism 22. In particular, when the light is poor, adjusting the height of the support column 212 makes it easier for the imaging mechanism 22 to focus, allowing the imaging mechanism 22 to observe the cell culture process from a better perspective.

[0063] Based on the preceding text and with reference to Figure 3 The cell culture device 10 can be installed on the top plate 213 of the base 21. To facilitate the imaging mechanism 22 to take pictures, the top plate 213 is provided with a shooting port 2131 that communicates with the aforementioned window 1311. The diameter of the shooting port 2131 can be larger than that of the window 1311, so that the imaging mechanism 22 has a larger shooting range.

[0064] In some specific embodiments, the imaging port 2131 is configured as a rectangular opening, so that the imaging mechanism 22 can easily capture images of multiple organ chips 113.

[0065] In some specific embodiments, the top plate 213 may be made of a transparent material at least at the position corresponding to the window 1311. This transparent material allows light to pass through, enabling the imaging mechanism 22 to perform imaging operations. The use of a transparent material here prevents the organ-on-a-chip 113 from being exposed, providing better protection for the organ-on-a-chip 113 and thereby improving the cell culture effect.

[0066] In some embodiments, please refer to Figure 3 The top plate 213 is provided with a slot 2132, and the cell culture equipment can be inserted into the top plate 213 along the slot 2132. The slot 2132 can be formed by recessing from the surface of the top plate 213, and the periphery of the slot 2132 can limit the cell culture equipment.

[0067] In some specific embodiments, an interlocking structure can be provided around the slot 2132, so that after the cell culture equipment is installed on the top plate 213, the interlocking structure can hold the cell culture equipment in place, thereby preventing the cell culture equipment from becoming loose. The specific type of interlocking structure is not limited; it can be, for example, a magnetic adsorption structure, a snap-fit ​​structure, or a connecting connector. Taking a snap-fit ​​structure as an example, a first snap-fit ​​can be provided around the slot 2132, and a second snap-fit ​​can be provided on the cell culture equipment. The second snap-fit ​​can cooperate with the first snap-fit ​​to achieve fixation.

[0068] In some embodiments, please refer to Figure 2 The imaging mechanism 22 includes an imaging drive component 221 and a camera component 222. The imaging drive component 221 is mounted on the base plate 211, and the camera component 222 is located at the output end of the imaging drive component 221, so that the imaging drive component 221 can drive the camera component 222 to move.

[0069] In some specific embodiments, the imaging drive component 221 can adopt a three-axis linkage structure. This component 221 may include three sets of linear motors arranged along the X, Y, and Z directions. The linkage of these three sets of linear motors enables the camera component 222 to move within a three-dimensional space, allowing the imaging mechanism 22 to capture better image information. Of course, in other embodiments, the imaging drive component 221 can also use gear transmission, lead screw transmission, belt transmission, or other methods to achieve the movement of the camera component 222 within a three-dimensional space.

[0070] Figure 4 A schematic diagram of the structure of a cell culture apparatus 10 provided according to an embodiment of this application is shown; Figure 5 A schematic diagram of another cell culture apparatus 10 provided according to an embodiment of this application is shown.

[0071] In the embodiments of this application, please refer to Figure 4 and Figure 5 The cell culture device 10 includes a culture box structure 11 and a gas distribution structure 12. The cell culture device 10 may also be equipped with a base 13 for the culture box structure 11 and the gas distribution structure 12.

[0072] The base 13 serves as a support structure for the culture structure 11 and the gas distribution structure 12. The culture box structure 11 and the gas distribution structure 12 can be mounted on the base 13. The base 13 can have an open structure on all four sides. For example, in some embodiments, the base 13 may include a substrate 131, a support frame 132, and a mounting plate 133. The substrate 131 and the mounting plate 133 can be flat and parallel. The support frame 132 connects the substrate 131 and the mounting plate 133 and can be disposed at opposite ends of the substrate 131.

[0073] It is understandable that setting the substrate 131 and mounting plate 133 as flat plates can structurally match the aforementioned bottom plate 211 and top plate 213, making the overall structure of the cultivation equipment simpler and more elegant.

[0074] Based on the preceding text and with reference to Figure 4 The substrate 131 is provided with the aforementioned window 1311, and the culture box structure 11 is installed at the window 1311, so that the imaging device 20 can perform imaging operations on the organ-on-a-chip 113 through the imaging port 2131 and the window 1311.

[0075] In light of the foregoing, to improve cell culture efficiency, please refer to... Figure 4 and Figure 5 Two windows 1311 can be spaced apart on the substrate 131. A culture box structure 11 can be set at each window 1311. Each culture box structure 11 can include multiple culture boxes 112. An organ-on-a-chip 113 is set in each culture box 112. This enables the culture of multiple organ-on-a-chips 113 in one culture cycle, which can greatly improve the culture efficiency.

[0076] Of course, in some other embodiments, a window 1311 may also be provided on the substrate 131, which can serve as a shared window 1311 for the two sets of culture box structures 11.

[0077] It is understandable that, regardless of whether two windows 1311, multiple windows 1311, or a single window 1311 are used, the camera aperture 2131 on the top plate 213 should always cover the location of the window 1311, allowing the window 1311 to be visible through the camera aperture 2131. For example, in Figure 4 and Figure 5In the example shown, two windows 1311 are spaced apart on the substrate 131, and both windows 1311 can be exposed from the shooting port 2131.

[0078] To form the two windows 1311, two spaced grooves 1312 can be provided on the side of the substrate 131 facing away from the top plate 213, into which the culture box structure 11 can be installed. The grooves 1312 can be designed similarly to the aforementioned slots 2132, allowing the culture box structure 11 to be inserted into them. The grooves 1312 extend through the substrate 131 on the side facing the top plate 213, thus forming a window 1311 within a portion of the grooves 1312.

[0079] In some embodiments, the area of ​​the recess 1312 may be larger than that of the window 1311, thereby making it easier for the culture box structure 11 to be installed into the recess 1312.

[0080] Understandably, when installing the culture box structure 11, after the culture box structure 11 is inserted into the groove 1312, the organ-on-a-chip 113 inside the culture box structure 11 needs to be exposed through the window 1311 so that the imaging mechanism 22 can acquire the culture status of the cells in the organ-on-a-chip 113. Therefore, to facilitate the imaging mechanism 22 to cover the location of each organ-on-a-chip 113 within a small range, the two sets of culture box structures 11 can be arranged facing each other in the two grooves 1312, so that the organ-on-a-chip 113 inside the culture box structure 11 can be exposed through the window 1311 facing each other.

[0081] Figure 6 A schematic diagram of a culture box structure 11 provided according to an embodiment of this application is shown;

[0082] Figure 7 A schematic diagram of the structure of a culture box 112 provided according to an embodiment of this application is shown; Figure 8 An exploded view of a culture box 112 provided according to an embodiment of this application is shown.

[0083] In some embodiments, please refer to Figures 6 to 8 The culture box structure 11 needs to include at least an organ-on-a-chip 113. In some embodiments, the culture box structure 11 may include a tray 111, a plurality of culture boxes 112 and a plurality of organ-on-a-chips 113. Each culture box 112 is provided with an organ-on-a-chip 113. The organ-on-a-chip 113 is located on the side of the culture box 112 facing the imaging mechanism 22. The tray 111 is provided with a plurality of mounting positions 1111. The plurality of culture boxes 112 can be correspondingly mounted on the plurality of mounting positions 1111.

[0084] As described above, the culture box structure 11 can be used to culture a group of cells, and the cell culture efficiency can be improved by setting multiple culture boxes 112 in the culture box structure 11.

[0085] In some embodiments, the mounting position 1111 is configured as a mounting port extending through the tray 111, into which the culture box 112 can be mounted. This mounting port is designed to facilitate the exposure of the organ-on-a-chip 113 through the window 1311, enabling the imaging mechanism 22 to perform imaging operations.

[0086] It can be seen that the mounting port on the tray 111, the window 1311 on the substrate 131, and the imaging port 2131 on the top plate 213 are correspondingly set, and the organ-on-a-chip 113 is within the imaging range of the imaging mechanism 22, thereby facilitating the imaging mechanism 22 to observe the cell culture status in real time.

[0087] In some specific embodiments, please refer to Figure 7 The end of the tray 111 has a force-applying part 1112, which can be a hollow ring structure, making it easy for the user to push the culture box structure 11 into the groove 1312.

[0088] In some specific embodiments, please refer to Figure 7 The end of the tray 111 has an irregular structure 1113, which can be curved, so that the tray 111 can engage with the corresponding structure in the groove 1312, thus preventing the tray 111 from falling out of the groove 1312.

[0089] In some embodiments, please refer to Figure 7 and Figure 8 The culture box 112 includes a box body 1121, a box cover 1122, and a partition plate 1123 disposed inside the box body 1121 to divide the space of the box body 1121 into multiple cavities 112a. The box cover 1122 is provided with an air pressure interface 1122a corresponding to the cavity 112a.

[0090] The number of cavities 112a in the culture box 112 can be set according to different cell types. It is understandable that the number of cavities 112a can be adapted to different cell types, such as lung cells, epidermal cells, and heart cells. For example, for lung cells, the box 1121 can have four cavities 112a. The function of the air pressure port 1122a is to create positive or negative pressure in the cavities 112a through ventilation, so that the culture medium can enter or flow out of the organ-on-a-chip 113.

[0091] In some embodiments, please refer to Figure 7 and Figure 8The housing 1121 has a mounting slot 1121a, in which the organ-on-a-chip 113 can be installed. It is understood that the organ-on-a-chip 113 has a chip interface that can communicate with each cavity 112a. Based on the foregoing description, the specific structure of various organ-on-a-chip 113 can be understood by referring to relevant technologies; further details are omitted in this application.

[0092] In some embodiments, please refer to Figure 4 and Figure 5 The gas distribution structure 12 includes a drive component and a gas distribution component 122. The drive component can output linear motion, rotational motion, etc. The gas distribution component 122 is mounted on the drive component. Under the drive of the drive component, the gas distribution component 122 can move along the output direction of the drive component. For example, when the drive component can output linear motion, the gas distribution component 122 can also move linearly.

[0093] The driving component in this application embodiment can adopt a variety of structural forms. In conjunction with the foregoing, in order to simplify the structure of the driving component and the culture device, the driving component can adopt a lifting driving component 121 that can output lifting motion. The lifting driving component 121 can better match the upper and lower structural forms of the cell culture device 10 and the imaging device 20, that is, the lifting driving component 121 can better match the vertical structure of the culture device for assembly.

[0094] The gas distribution component 122 is a structure in the gas distribution structure 12 that needs to be connected to the organ-on-a-chip 113. The gas distribution component 122 is provided with a passageway, allowing it to connect to or disconnect from the organ-on-a-chip 113. The lifting drive component 121 can drive the gas distribution component 122 closer to or further away from the organ-on-a-chip 113. It is understood that when the gas distribution component 122 is connected to the organ-on-a-chip 113, the culture device can deliver culture medium into the organ-on-a-chip 113; when the gas distribution component 122 is disconnected from the organ-on-a-chip 113, the culture device can interrupt the delivery of culture medium.

[0095] In this embodiment, the lifting drive component 121 can drive the gas distribution component 122 to move in a straight line. Under the drive of the lifting drive component 121, the gas distribution component 122 can move closer to or further away from the organ-on-a-chip 113, thereby realizing the connection and disconnection between the passage in the gas distribution component 122 and the organ-on-a-chip 113. The gas distribution component 122 can act as a pipeline, and the lifting drive component 121 reduces the requirements of the mechanism, thereby simplifying the structure of the culture equipment.

[0096] Based on the two descriptions of culture medium delivery methods above and the relevant description of the culture box structure 11, it can be seen that the embodiments of this application mainly use the method of storing culture medium in the culture box 112 and delivering the culture medium to the organ-on-a-chip 113 by forming gas pressure. Therefore, this will be explained in the following embodiments. In other words, the following embodiments mainly use the connection and disconnection between the gas distribution component 122 and the culture box 112 as an example to explain the various functions of the gas distribution structure 12.

[0097] Figure 9 A schematic diagram of the structure of a lifting drive assembly 121 according to an embodiment of this application is shown; Figure 10 This paper shows a structural schematic diagram of a lifting drive assembly 121 provided according to an embodiment of the present application from another angle.

[0098] In some embodiments, please refer to Figure 4 , Figure 5 , Figure 9 and Figure 10 The lifting drive assembly 121 includes a drive motor 1211, a transmission assembly 1212, and a pusher 1213.

[0099] The drive motor 1211 can be a servo motor to precisely control the output displacement of the lifting drive assembly 121. Of course, in some embodiments, the drive motor 1211 can also be a stepper motor or the like.

[0100] The transmission assembly 1212 can convert the motion of the drive motor 1211. The transmission assembly 1212 is connected to the output end of the drive motor 1211, specifically, the transmission assembly 1212 can be linked to the output shaft of the drive motor 1211. The transmission assembly 1212 is arranged laterally. To simplify the structure and layout, and in conjunction with the previous description of the base 13, the drive motor 1211 and the transmission assembly 1212 can be mounted on the mounting plate 133 of the base 13.

[0101] The pusher 1213 is arranged vertically and can move vertically under the action of the transmission assembly 1212. The pusher 1213 can form the output end of the lifting drive assembly 121. The pusher 1213 can act on the gas distribution assembly 122 and cause the gas distribution assembly 122 to move vertically.

[0102] To clearly define the meanings of "horizontal" and "vertical" as mentioned above, the following is a combination of... Figure 4 The coordinate system in the diagram is explained below. Please refer to [reference needed]. Figure 4The base 13 has a rectangular parallelepiped structure. Both the base plate 131 and the mounting plate 133 of the base 13 are located in the XY plane. Any straight line within the XY plane defines the direction as transverse. Both sets of culture box structures 11 are arranged along the X direction, which is one type of transverse direction. For ease of description, the transmission assembly 1212 can also be arranged along the X direction and mounted on the mounting plate 133. The support frame 132 is located in the YZ plane, where the Z direction indicates the vertical direction, which is perpendicular to the aforementioned transverse direction.

[0103] Therefore, it can be seen that in the embodiment of this application, the lifting drive component 121, which serves as the power source, has a drive motor 1211 and a transmission component 1212 that performs motion conversion function arranged in a horizontal direction, while the pusher 1213, which serves as the output end, is arranged in a vertical direction. This arrangement can make full use of the internal space of the base 13, thereby simplifying the structure of the cultivation equipment.

[0104] In some embodiments, please refer to Figures 9 to 10 The transmission assembly 1212 includes a transmission shaft 1212a and a transmission protrusion 1212b. The transmission shaft 1212a is connected to the output end of the drive motor 1211, and the transmission protrusion 1212b is disposed on the transmission shaft 1212a and can rotate with the transmission shaft 1212a.

[0105] After the drive motor 1211 is started, the output shaft of the drive motor 1211 can drive the transmission shaft 1212a to rotate. The transmission protrusion 1212b can be a block structure including irregular shapes such as ellipse. When the transmission shaft 1212a drives the transmission protrusion 1212b to rotate in the vertical range, based on the irregular arrangement of the transmission protrusion 1212b, the transmission protrusion 1212b can present an undulating motion posture in the vertical direction. Thus, when the transmission protrusion 1212b acts on the pusher 1213, the pusher 1213 can form a linear motion in the vertical direction.

[0106] In addition to adopting a block-shaped structure, the transmission protrusion 1212b can also adopt a plate-shaped structure or other structures. For example, the transmission protrusion 1212b can be an arc-shaped blade-type structure.

[0107] In some embodiments, at least one side of the transmission protrusion 1212b is an arc surface, which can act on the pusher 1213. It is understood that the outer edge of the arc surface is curved, and the arc surface needs to adopt an eccentric design, so that during the rotation of the transmission protrusion 1212b, the arc surface can push the pusher 1213 to perform lifting and lowering movements.

[0108] In some embodiments, please refer to Figures 9 to 10The lifting drive assembly 121 also includes a drive base 1214, on which the drive motor 1211 and the transmission assembly 1212 can be mounted. The drive base 1214 can be mounted on the mounting plate 133.

[0109] The drive base 1214 has a vertical moving cavity 1214a, and the pusher 1213 is disposed in the moving cavity 1214a and can move along the moving cavity 1214a.

[0110] It is understood that the moving cavity 1214a can be a vertical cavity 112a structure or a vertical channel structure. In a free state, the pusher 1213 can move within the moving cavity 1214a.

[0111] In some specific embodiments, to prevent the pusher 1213 from detaching from the moving cavity 1214a, an anti-detachment structure that can limit the detachment of the pusher 1213 can be provided on the drive seat 1214. The anti-detachment structure can be one of a magnetic adsorption structure or an elastic structure. Taking the elastic structure as an example, the anti-detachment structure can be a compression spring or a torsion spring, or a material ring with deformation characteristics. The compression spring, torsion spring, or material ring can be arranged around the pusher 1213 so as to form a pulling force on the pusher 1213, thereby making it difficult for the pusher 1213 to detach from the moving cavity 1214a.

[0112] In some embodiments, please refer to Figures 9 to 10 The drive base 1214 includes a first mounting portion 1214b and a second mounting portion 1214c having a receiving cavity 1214c1. The first mounting portion 1214b and the second mounting portion 1214c are arranged laterally at a distance from each other and are arranged opposite to each other. The drive motor 1211 is mounted on the first mounting portion 1214b, the drive shaft 1212a passes through the second mounting portion 1214c, and the drive protrusion 1212b is received in the receiving cavity 1214c1.

[0113] Specifically, the first mounting part 1214b can be a plate 1214b1, which is mounted vertically. The drive motor 1211 can be mounted on one side of the plate 1214b1, and the output shaft of the drive motor 1211 can pass through the plate 1214b1. The second mounting part 1214c can be a frame structure formed by a set of enclosing plates, wherein the frame structure has two oppositely arranged side plates 1214c2, and the drive shaft 1212a can pass through the two side plates 1214c2 in sequence after being connected to the output shaft. Thus, the first mounting part 1214b and the second mounting part 1214c can support the drive motor 1211 and the drive shaft 1212a, and enable the drive motor 1211 and the drive shaft 1212a to rotate.

[0114] In the above embodiment, the transmission protrusion 1212b is housed in a receiving cavity 1214c1 formed by the second mounting portion 1214c. The second mounting portion 1214c can be a frame structure, which can protect the transmission protrusion 1212b and extend the effective cycle between the transmission protrusion 1212b and the pusher 1213. Of course, based on protecting the transmission protrusion 1212b, the second mounting portion 1214c can be configured as a surrounding structure or a semi-surrounding structure, thereby preventing dust and other contaminants from entering the receiving cavity 1214c1 and providing better protection for the transmission between the transmission protrusion 1212b and the pusher 1213.

[0115] In some embodiments, please refer to Figures 9 to 10 The drive seat 1214 also includes a third mounting part 1214d, which is located at the bottom of the second mounting part 1214c. The moving cavity 1214a passes through the third mounting part 1214d, and the third mounting part 1214d is provided with a plurality of mounting holes 1214d1.

[0116] The third mounting part 1214d is located at the bottom of the drive base 1214, and the drive base 1214 can be fixedly mounted to the mounting plate 133 by means of the mounting holes 1214d1 on the third mounting part 1214d.

[0117] In some embodiments, please refer to Figure 10 The end of the pusher 1213 near the transmission protrusion 1212b forms a force-bearing platform 1213a, and the transmission protrusion 1212b can act on the force-bearing platform 1213a.

[0118] As mentioned above, the transmission protrusion 1212b can adopt an irregular structural form. Therefore, when the transmission protrusion 1212b periodically acts on the pusher 1213, wear will occur between the transmission protrusion 1212b and the pusher 1213. By forming a force-bearing platform 1213a at the end of the pusher 1213, the contact area between the transmission protrusion 1212b and the pusher 1213 can be increased, thereby reducing wear.

[0119] In some embodiments, please refer to Figure 9 The lifting drive assembly 121 also includes a displacement monitoring assembly 1215, which is used to detect the rotation angle of the drive shaft 1212a.

[0120] Based on the setting of the detection component, the rotation angle of the drive shaft 1212a can be accurately monitored, and then the rotation angle of the drive protrusion 1212b can be obtained. This allows the displacement distance of the pusher 1213 to be obtained, and further, the connection and disconnection between the gas distribution component 122 and the culture box 112 can be precisely controlled.

[0121] In some specific embodiments, the displacement monitoring component 1215 includes at least one of a magnetic encoder, a photoelectric encoder, or a Hall sensor.

[0122] In some embodiments, please refer to Figure 9 and Figure 10 The second mounting portion 1214c forms a movable cavity 1214a below the receiving cavity 1214c1. Both the movable cavity 1214a and the receiving cavity 1214c1 are formed by the second mounting portion 1214c, which simplifies the structure of the second mounting portion 1214c and makes the second mounting portion 1214c more compact in structure while saving materials.

[0123] In some embodiments, please refer to Figure 4 and Figure 5 The gas distribution structure 12 also includes a guide component 123, which is arranged along the output direction of the lifting drive component 121, and the gas distribution component 122 can move along the guide component 123.

[0124] The guide component 123 enables the partition component to move more smoothly and prevents the gas distribution component 122 from tilting.

[0125] In some specific embodiments, the guide component 123 can be disposed at both ends of the gas distribution component 122 in the lateral direction, so that the gas distribution component 122 can be guided by the guide component 123 on both sides in the X direction, which can prevent the gas distribution component 122 from being too high at one end and too low at the other end.

[0126] In some specific embodiments, the guide assembly 123 includes a guide rod 1231 and a guide block 1232, the guide block 1232 being movably disposed on the guide rod 1231, and the gas distribution assembly 122 being connected to the guide block 1232.

[0127] The guide rod 1231 can be a smooth rod. After the guide block 1232 is connected to the air distribution component 122, the two can become a whole and move up and down, which can ensure the smoothness of the movement while improving the structural strength of the air distribution component 122.

[0128] In some embodiments, please refer to Figure 4 and Figure 5 The guide assembly 123 also includes a reset member 1233, which can be a spring, compression spring, etc. The reset member 1233 can be connected between the base 13 and the guide block 1232. The reset member 1233 is used to drive the gas distribution assembly 122 to move away from the organ chip 113.

[0129] The aforementioned guide rod 1231, guide block 1232, and reset member 1233 can all be installed on the base 13, for example, on the support frame 132 of the base 13.

[0130] Therefore, it can be understood that the movement process of the gas distribution component 122 can be briefly described as follows: After the drive motor 1211 is started, the transmission shaft 1212a drives the transmission protrusion 1212b to rotate. The transmission protrusion 1212b can act on the pusher 1213 and cause the pusher 1213 to push the gas distribution component 122 closer to the culture box 112. During this process, the reset member 1233 gradually accumulates elastic restoring force. When it is necessary to drive the gas distribution component 122 to separate from the culture box 112, the drive motor 1211 is reversed. Under the action of the reset member 1233, the pusher 1213 can drive the transmission protrusion 1212b to gradually reset, thereby reducing the load pressure on the drive motor 1211. On the other hand, due to the driving effect of the reset member 1233 on the guide block 1232, the pusher 1213 tends to move away from the culture box 112 when the drive motor 1211 is not started. This can avoid damage to the culture box 112 due to misoperation and is also beneficial for the culture box structure 11 to be assembled onto the base 13.

[0131] In some embodiments, please refer to Figure 4 and Figure 5 The gas distribution assembly 122 is provided with a force-receiving member 124, which can cooperate with the aforementioned pusher 1213. The force-receiving member 124 can be fixedly connected to the gas distribution assembly 122. The provision of the force-receiving member 124 can shorten the movement stroke of the pusher 1213, which is beneficial to simplifying the structural composition of the transmission assembly 1212, such as reducing the size of the transmission protrusion 1212b.

[0132] As can be seen from the following embodiments, the air distribution assembly 122 may include an air venting base 1221, and the aforementioned force-bearing member 124 may be connected to the air venting base 1221.

[0133] In the above embodiments, the pusher 1213 and the force-receiving member 124 can adopt a rod-shaped structure. In order to improve the transmission effect between the two, the contact area between the pusher 1213 and the force-receiving member 124 can be designed to be large. For example, a platform structure similar to the aforementioned force-receiving platform 1213a can be provided at the end of the force-receiving member 124 near the pusher 1213.

[0134] In some embodiments, please refer to Figure 4 and Figure 5The gas distribution assembly 122 includes a venting base 1221 and a control valve 1222. The venting base 1221 has multiple passages inside. The control valve 1222 is connected to the venting base 1221 and is connected to at least a portion of the multiple passages for controlling the opening and closing of some of the passages.

[0135] The ventilation substrate 1221 can be larger than the culture box structure 11 in terms of structure. The projection of the ventilation substrate 1221 along the Y direction can be larger than the projection of the culture box structure 11 along the Y direction, thereby enabling the gas distribution component 122 to be connected to each culture box 112.

[0136] It is understandable that the passage is formed inside the venting substrate 1221. To design a venting substrate 1221 that includes the passage, it can be manufactured using injection molding. Depending on the required passage, different inserts can be used during injection molding. These inserts have the same external shape as the passage. After injection molding, the corresponding passage can be formed by pulling out the inserts.

[0137] It is understood that the control valve 1222 may include a valve body and a valve core. The opening degree of the control valve 1222 can be changed by the movement of the valve core within the valve body. After the control valve 1222 is connected to the venting base 1221, the passage in the control valve 1222 needs to be connected to the passage in the venting base 1221. Specifically, the passage in the control valve 1222 can be connected to the passage and become part of the passage. Thus, the control action of the control valve 1222 can realize the on / off control and flow control of a certain passage.

[0138] It should be noted that the opening and closing of the passage includes the safe opening of the passage, the complete closure of the passage, and the intermediate state in which the degree of opening and closing can be adjusted. The on / off control and flow control of a certain passage can be achieved by the intervention adjustment of the passage through the control valve 1222.

[0139] In this embodiment, the gas distribution component 122 is a combination structure of a control valve 1222 and a ventilation substrate 1221. Through the interventional control of the passage by the control valve 1222, the on / off control and flow control of different passages can be realized, so that the ventilation substrate 1221 can selectively connect to different culture boxes 112 / organ-on-a-chip 113, thereby realizing individual control of ventilation for each culture box 112 / organ-on-a-chip 113, thereby realizing the on / off control and flow control of the culture medium for each culture box 112 / organ-on-a-chip 113, which can improve the culture effect of organ-on-a-chip 113.

[0140] In some embodiments, the ventilation substrate 1221 includes at least one main passage 1221a and multiple sets of branch passages, which are respectively connected to the main passage 1221a, and the control valve 1222 is connected to the branch passages.

[0141] As described above, the aeration substrate 1221 can cover each culture box 112. The aeration substrate 1221 is equivalent to a common air intake structure for each culture box 112. Gas can pass through the aeration substrate 1221 and then enter each culture box 112. In order for the gas supply device in the culture equipment to supply gas to each culture box 112, the aeration substrate 1221 needs to be provided with at least one main passage 1221a. During the operation of the gas supply device, the main passage 1221a always contains gas. Next, in order to allow the gas in the main channel 1221a to enter each culture box 112, a set of branch channels is set for each culture box 112. The design of each set of branch channels being connected to the main channel 1221a allows each set of branch channels to correspond to the corresponding culture box 112. At this time, by setting control valves 1222 on the branch channels, the on / off and flow control of each branch channel can be realized, thereby realizing the on / off and flow control of the culture medium in the culture box 112 / organ-on-a-chip 113.

[0142] In some embodiments, each group of branch passages includes multiple branch passages 1221b, and control valves 1222 are provided for each group of branch passages, with the number of control valves 1222 being the same as the number of branch passages 1221b.

[0143] As one design option, the number of branch passages 1221b can be the same as the number of cavities 112a in the culture box 112. Each branch passage 1221b is equipped with a corresponding control valve 1222, thereby controlling the flow of gas into each cavity 112a. Figure 7 and Figure 8 In the example shown, five air pressure ports 1122a are formed on the culture box 112. Correspondingly, the number of branch passages 1221b can be five, and the number of control valves 1222 can also be five.

[0144] Figure 11 A schematic diagram of the structure of a ventilated substrate 1221 provided according to an embodiment of this application is shown; Figure 12 A perspective view of a ventilation substrate 1221 provided according to an embodiment of this application is shown.

[0145] In some embodiments, please refer to Figure 11 and Figure 12The ventilation substrate 1221 has multiple ventilation inlets 1221c at one end along its length and multiple ventilation outlets 1221d at the other end along its length. The main passage 1221a connects the ventilation inlets 1221c and the ventilation outlets 1221d.

[0146] The length direction here is the X direction. Setting the main passage 1221a along the length direction of the aeration substrate 1221 can make the main passage 1221a correspond to each culture box 112.

[0147] In some embodiments, the side of the ventilation substrate 1221 is provided with a plurality of branch outlets 1221e, and the branch passages are connected between the branch outlets 1221e and the main passage 1221a.

[0148] Here, "side" refers to the side of the aeration substrate 1221 facing the culture box 112. The branch outlet 1221e needs to be connected to the air pressure interface 1122a on the culture box 112, so as to form a connection between the aeration substrate 1221 and the culture box 112.

[0149] In some other embodiments, in order to form the main passage 1221a, the ventilation substrate 1221 may be provided with a plurality of ventilation inlets 1221c at one end along its length direction, and the other end of the ventilation substrate 1221 along its length direction is a closed end, and the main passage 1221a extends from the ventilation inlets 1221c to the closed end.

[0150] In this embodiment, the control valve 1222 can be selected from components such as a solenoid valve or a miniature solenoid valve.

[0151] In the description of this application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application.

[0152] In the description of this application, it should be understood that the terms "comprising" and "having" and any variations thereof used in the embodiments of this application are intended to cover non-exclusive inclusion. For example, a process, method, system, product, or device that includes a series of steps or units is not necessarily limited to those steps or units that are explicitly listed, but may include other steps or units that are not explicitly listed or that are inherent to such process, method, product, or device.

[0153] Unless otherwise expressly specified and limited, the terms "installation," "connection," "linking," "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the connection within two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this application according to the specific circumstances. Furthermore, the terms "first," "second," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated.

[0154] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A gas distribution assembly, characterized in that, include: A ventilated substrate, wherein multiple passages are formed inside the ventilated substrate; And a control valve, the control valve being connected to the venting body and being connected to at least a portion of the plurality of said passages, for controlling the opening and closing of a portion of said passages.

2. The gas distribution assembly according to claim 1, characterized in that, The ventilation substrate includes at least one main passage and multiple sets of branch passages, with each set of branch passages connected to the main passage, and the control valve connected to one of the branch passages.

3. The gas distribution assembly according to claim 2, characterized in that, The ventilation substrate has multiple ventilation inlets at one end along its length and multiple ventilation outlets at the other end along its length. The main passage connects the ventilation inlets and the ventilation outlets.

4. The gas distribution assembly according to claim 3, characterized in that, The side of the ventilation substrate is provided with multiple branch outlets, and the branch outlets are connected between the branch outlets and the main channel.

5. The gas distribution assembly according to claim 2, characterized in that, The ventilation substrate has multiple ventilation inlets at one end along its length, and the other end along its length is a closed end. The main passage extends from the ventilation inlets to the closed end.

6. The gas distribution assembly according to claim 2, characterized in that, Each group of branch passages includes multiple branch passages, and the control valves are provided for each group of branch passages, and the number of control valves is the same as the number of branch passages.

7. The gas distribution assembly according to any one of claims 1 to 6, characterized in that, The control valve includes a solenoid valve.

8. A gas-distributing structure, characterized in that, include: Driver components; And the gas distribution assembly according to any one of claims 1 to 7, wherein the driving assembly is used to drive the gas distribution assembly to move along the output direction of the driving assembly.

9. A cell culture device, characterized in that, include: Culture box structures, including organ-on-a-chip; And the gas distribution structure of claim 8, wherein the gas distribution component in the gas distribution structure can be connected to or disconnected from the organ-on-a-chip.

10. A cultivation device, characterized in that, Includes the cell culture apparatus as described in claim 9.

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