Organ chip holder and organ chip device

Abstract

The application relates to an organ chip clamp and an organ chip device. The organ chip clamp comprises a base and a cover plate. The base is provided with a placement area for placing a chip body, and the placement area is provided with a first pneumatic interface for communicating with a first gas inlet and outlet of the chip body; the first pneumatic interface is used for being connected to a gas pressure vacuum controller. The cover plate is connected with the base and is used for abutting to one side of the chip body away from the base, the cover plate is provided with a first sealing piece for sealing a liquid inlet and outlet of the chip body, and the cover plate is also provided with a second pneumatic interface for communicating with a second gas inlet and outlet of the chip body. The second pneumatic interface is used for being connected to the gas pressure vacuum controller. The organ chip clamp and the organ chip device can reduce experimental result error.

Description

Technical Field

[0001] This application relates to the field of organ-on-a-chip technology, and in particular to organ-on-a-chip fixtures and organ-on-a-chip devices. Background Technology

[0002] Organ-on-a-chip technology, as a significant breakthrough in the biomedical field, provides innovative tools for disease mechanism research and drug development. For example, the lung organ-on-a-chip is a representative model that can simulate the air-blood barrier structure and physiological function of the alveoli, realistically reflecting the physiological and pathological characteristics of the lungs, such as viral infection, fibrosis, or inflammatory responses, making it an ideal platform to replace traditional research methods.

[0003] Organ-on-a-chip devices typically have multiple chambers for culturing cells or applying pressure. Correspondingly, each chamber has a liquid inlet / outlet for introducing cell suspension, or a gas inlet / outlet for applying pressure. During experiments, the liquid inlet / outlet needs to be sealed, and the gas inlet / outlet needs to be connected to a pressure / vacuum controller.

[0004] Currently, in experiments, operators typically need to manually plug the liquid inlets and outlets of the organ-on-a-chip using plugs, and manually connect the gas inlets and outlets to the gas pipes of the pressure vacuum controller. However, each organ-on-a-chip usually has multiple liquid inlets and outlets and multiple gas inlets and outlets. As the number of organ-on-a-chip samples increases in groups, operators need to plug dozens of liquid inlets and outlets and connect dozens of gas inlets and outlets each time, which is very easy to cause errors, resulting in the failure of sealing some liquid inlets and outlets or the failure of connecting some gas inlets and outlets, thus causing deviations in experimental results. Utility Model Content

[0005] Therefore, it is necessary to provide an organ-on-a-chip fixture and organ-on-a-chip device to address the technical problems of the current cumbersome and error-prone operation of manually sealing the liquid inlet and outlet of the organ-on-a-chip and manually connecting the gas inlet and outlet.

[0006] In a first aspect, this application provides an organ-on-a-chip fixture, comprising:

[0007] The base has a placement area for placing the chip body, and the placement area has a first pneumatic interface for communicating with a first gas inlet and outlet of the chip body. The first pneumatic interface is used to connect to a pneumatic vacuum controller.

[0008] A cover plate is connected to the base and is used to abut against the side of the chip body away from the base. The cover plate is provided with a first sealing element for sealing the liquid inlet and outlet of the chip body. The cover plate is also provided with a second pneumatic interface for communicating with a second gas inlet and outlet of the chip body. The second pneumatic interface is used to connect to a pneumatic vacuum controller.

[0009] The technical solution will be further explained below:

[0010] In one embodiment, the placement area has a receiving groove for accommodating the chip body, and the first pneumatic interface is provided on the bottom wall of the receiving groove.

[0011] In one embodiment, the organ-on-a-chip fixture further includes a first pneumatic connector, which is connected to a first pneumatic interface, and the first pneumatic interface is connected to the pneumatic vacuum controller through the first pneumatic connector.

[0012] In one embodiment, the base is further provided with a first connection port communicating with the first pneumatic interface, and the first pneumatic connector is connected to the first connection port.

[0013] In one embodiment, the placement area is further provided with an observation window for observing the chip body.

[0014] In one embodiment, the cover plate is provided with a plurality of first seals, which are used to seal a plurality of liquid inlets and outlets on the chip body in a one-to-one correspondence.

[0015] In one embodiment, the first seal includes a plug for insertion into the liquid inlet / outlet on the chip body; or...

[0016] The first sealing element includes a sealing ring, which is used to surround the outer periphery of the liquid inlet and outlet and to engage with the chip body under pressure.

[0017] In one embodiment, the cover plate has a plurality of second pneumatic interfaces, which are used to connect one-to-one with a plurality of second gas inlets and outlets on the chip body.

[0018] In one embodiment, the organ-on-a-chip fixture further includes a pneumatic connector having a pressure chamber and a second connection port communicating with the pressure chamber. The pneumatic connector is connected to the cover plate, and the pressure chamber is communicating with all the second pneumatic interfaces. The second connection port is used to connect to a pneumatic vacuum controller.

[0019] In one embodiment, the organ-on-a-chip fixture further includes a second pneumatic connector connected to the second connection port, and the second connection port is connected to the pneumatic vacuum controller via the second pneumatic connector.

[0020] In one embodiment, the base is provided with a first pneumatic sealing ring, which surrounds the periphery of the first pneumatic interface and is used to seal the gap between the first pneumatic interface and the first gas inlet / outlet.

[0021] In one embodiment, the base is further provided with a gasket, and the height of the gasket protruding from the base is equal to the height of the first pneumatic seal protruding from the base.

[0022] In one embodiment, the cover plate is provided with a second pneumatic sealing ring, which surrounds the periphery of the second pneumatic interface and is used to seal the gap between the second pneumatic interface and the second gas inlet / outlet.

[0023] In one embodiment, one of the base and the cover plate is provided with a positioning post, the positioning post having a threaded hole; the other is provided with a positioning countersunk hole, the positioning countersunk hole having a connecting hole through it, the positioning post being inserted into the positioning countersunk hole, and the threaded hole and the connecting hole being aligned. The organ-on-a-chip fixture also includes a threaded connector, the threaded connector being inserted into the connecting hole and threadedly engaged with the threaded hole.

[0024] Secondly, this application also provides an organ-on-a-chip device, including a chip body and the aforementioned organ-on-a-chip fixture.

[0025] In one embodiment, the chip body includes at least one chip structure, each chip structure including an upper cavity, a middle cavity and a lower cavity, a porous membrane is provided between the upper cavity and the middle cavity, and a non-porous membrane is provided between the middle cavity and the lower cavity;

[0026] Each lower cavity is connected to a pneumatic channel, and the other end of all pneumatic channels is connected to a first gas inlet and outlet; each upper cavity is connected to a first liquid inlet and a first liquid outlet, as well as a second gas inlet and outlet; each middle cavity is connected to a second liquid inlet and a second liquid outlet.

[0027] In one embodiment, there are multiple chip structures, and each chip structure is spaced apart on the chip body.

[0028] In the aforementioned organ-on-a-chip fixture, a first pneumatic interface is provided in the placement area of ​​the base, and a second pneumatic interface is provided in the cover plate, which also has a first sealing element. Thus, by placing the chip body on the placement area of ​​the base, and then connecting the cover plate to the base and abutting against the side of the chip body away from the base, the first sealing element blocks the liquid inlet and outlet of the chip body while simultaneously connecting the first pneumatic interface to the first gas inlet and outlet of the chip body, and the second pneumatic interface to the second gas inlet and outlet of the chip body. This, in turn, connects to a pressure vacuum controller via the first and second pneumatic interfaces, allowing control of the air pressure in the upper and lower chambers of the chip body. This creates a pressure difference across the porous membrane containing the cell layer, causing deformation and simulating alveolar respiratory movements. Compared to traditional experimental methods that require manual insertion of endotracheal tubes and plugs, the organ-on-a-chip fixture of this application eliminates the need to manually plug each of the numerous liquid inlet and outlet of the chip body, and to individually connect each of the numerous gas inlet and outlet to endotracheal tubes. Simply connect the first pneumatic interface and the second pneumatic interface to the pneumatic vacuum controller. This can greatly simplify the experimental operation steps and reduce the experimental result errors caused by manually inserting air tubes or plugs. Attached Figure Description

[0029] The accompanying drawings, which form part of this application, are used to provide a further understanding of this application. The illustrative embodiments of this application and their descriptions are used to explain this application and do not constitute an undue limitation of this application.

[0030] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0031] Furthermore, the accompanying drawings are not drawn to a 1:1 scale, and the relative dimensions of the various components are shown as examples only and not necessarily to scale. In the accompanying drawings:

[0032] Figure 1 This is a schematic diagram of the structure of an organ-on-a-chip device according to one embodiment.

[0033] Figure 2 This is an exploded view of an organ-on-a-chip device according to one embodiment.

[0034] Figure 3 This is a perspective view of the chip body of an organ-on-a-chip device according to an embodiment.

[0035] Figure 4 This is a cross-sectional view of the chip body of an organ-on-a-chip device according to an embodiment.

[0036] Figure 5 This is a schematic diagram of the base of an organ-on-a-chip device according to one embodiment.

[0037] Figure 6 This is a schematic diagram of the cover plate of an organ-on-a-chip device according to one embodiment.

[0038] Figure 7 This is a schematic diagram of the pneumatic connector of an organ-on-a-chip device according to one embodiment.

[0039] Explanation of reference numerals in the attached figures:

[0040] 10. Organ-on-a-chip fixture; 11. Base; 111. Receiving slot; 112. First pneumatic interface; 113. First connection port; 114. Observation window; 115. First pneumatic sealing ring; 116. Gasket; 117. Positioning post; 118. Threaded hole; 12. Cover plate; 121. Second pneumatic interface; 122. First sealing element; 123. Second pneumatic sealing ring; 124. Positioning countersunk hole; 125. Connection hole; 20. Chip body; 21. Upper cavity ; 211, Second gas inlet / outlet; 212, First liquid inlet; 213, First liquid outlet; 22, Middle cavity; 221, Second liquid inlet; 222, Second liquid outlet; 23, Lower cavity; 231, First gas inlet / outlet; 232, Pneumatic channel; 24, Porous membrane; 25, Non-porous membrane; 30, First pneumatic connector; 40, Second pneumatic connector; 50, Pneumatic connector; 51, Air pressure chamber; 52, Second connection port; 60, Threaded connector. Detailed Implementation

[0041] To make the above-mentioned objectives, features, and advantages of this application more apparent and understandable, the specific embodiments of this application are described in detail below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of this application. However, this application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of this application. Therefore, this application is not limited to the specific embodiments disclosed below.

[0042] In the description of this application, it should be understood that if terms such as "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential" appear, these terms 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.

[0043] Furthermore, where the terms "first" and "second" appear, these terms are for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined with "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, where the term "multiple" appears, "multiple" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0044] In this application, unless otherwise expressly specified and limited, the terms "installation," "connection," "joining," and "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 mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components, unless otherwise expressly limited. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0045] In this application, unless otherwise expressly specified and limited, the use of descriptions such as "above" or "below" the second feature indicates that the first and second features are in direct contact or indirect contact via an intermediate medium. Furthermore, "above," "on top of," and "over" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. Similarly, "below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0046] It should be noted that if an element is referred to as being "fixed to" or "set on" another element, it can be directly on the other element or there may be an intervening element. If an element is considered to be "connected to" another element, it can be directly connected to the other element or there may be an intervening element. If so, the terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used in this application are for illustrative purposes only and do not represent the only possible implementation.

[0047] See Figure 1 as well as Figure 2 , Figure 1 A schematic diagram of the structure of an organ-on-a-chip device according to an embodiment of this application is shown. Figure 2An exploded view of the structure of an organ-on-a-chip device according to an embodiment of this application is shown. Specifically, the organ-on-a-chip device of one embodiment includes a chip body 20 and an organ-on-a-chip fixture 10, wherein the chip body 20 is used to simulate the physiological functions and mechanical movements of an organ, and the organ-on-a-chip fixture 10 is used to fix the chip body 20.

[0048] For example, in one embodiment, the chip body 20 is a lung organ-on-a-chip for simulating alveolar respiratory movements. In other embodiments, the chip body 20 may also be an organ-on-a-chip for simulating the physiological functions of other organs, such as an intestinal chip for simulating intestinal peristalsis or a tracheal chip for simulating tracheal airflow. For ease of description, this embodiment uses a lung organ-on-a-chip as an example.

[0049] Specifically, see Figure 3 as well as Figure 4 In one embodiment, the chip body 20 includes at least one chip structure, each chip structure including an upper cavity 21, a middle cavity 22, and a lower cavity 23. The upper cavity 21 and the middle cavity 22 are used for culturing cells, such as alveolar cells or vascular cells, while the lower cavity 23 is used for applying air pressure or vacuum.

[0050] Furthermore, a porous membrane 24 is provided between the upper cavity 21 and the middle cavity 22, which serves as a culture substrate for cells. A non-porous membrane 25 is provided between the middle cavity 22 and the lower cavity 23. By creating a pressure difference between the lower cavity 23 and the upper cavity 21, the non-porous membrane 25 can be deformed, thereby pulling the porous membrane 24 and the cell layer on the porous membrane 24 to deform, thus realizing the respiratory movement of the alveoli.

[0051] Furthermore, each lower cavity 23 is connected to a pneumatic channel 232, and the other end of all pneumatic channels 232 is connected to a first gas inlet / outlet 231. Through the first gas inlet / outlet 231, air pressure or vacuum can be applied to the lower cavity 23, thereby creating a pressure difference between the lower cavity 23 and the upper cavity 21.

[0052] Each upper cavity 21 is connected to a first liquid inlet 212, a first liquid outlet 213, and a second gas inlet / outlet 211. Cell suspension can be infused into the upper cavity 21 through the first liquid inlet 212, allowing cells in the suspension to be seeded onto the side of the non-porous membrane 25 facing the upper cavity 21. The cell suspension can be discharged from the upper cavity 21 through the first liquid outlet 213. Gas pressure or a vacuum can be applied to the upper cavity 21 through the second gas inlet / outlet 211, creating a pressure difference between the upper cavity 21 and the lower cavity 23.

[0053] Each cavity 22 is connected to a second liquid inlet 221 and a second liquid outlet 222. Cell suspension can be injected into the cavity 22 through the second liquid inlet 221, so that cells in the cell suspension can be seeded on the side of the non-porous membrane 25 facing the cavity 22. Cell suspension can be discharged from the cavity 22 through the first liquid outlet 213.

[0054] It should be noted that the number of chip structures in the chip body 20 can be one or more. When there are multiple chip structures in the chip body 20, the multiple chip structures are arranged at intervals on the chip body, which can simulate multiple alveolar tissues at the same time, thereby improving experimental efficiency. For example, Figure 3 As shown, the chip structure has three components, allowing for the simultaneous simulation of three alveolar tissues. Correspondingly, the upper surface of the chip body 20 has three second gas inlets / outlets 211, three first liquid inlets 212, three first liquid outlets 213, three second liquid inlets 221, and three second liquid outlets 222 (hereinafter referred to as liquid inlets / outlets). The lower surface of the chip body 20 has one first gas inlet / outlet 231. The pneumatic channels 232 of the three lower cavities 23 all converge at the same first gas inlet / outlet 231, thus allowing for the inflation and deflation of the three lower cavities 23 through a single first gas inlet / outlet 231. Understandably, the number of chip structures for each organ-on-a-chip can also be two, four, five, or more, etc., without limitation.

[0055] Specifically, in the traditional experimental process, the experimenter needs to manually plug the various liquid inlets and outlets of the organ-on-a-chip using plugs, and manually connect the trachea and various gas inlets and outlets. However, as mentioned above, each chip body 20 has four gas inlets and outlets and twelve liquid inlets and outlets that need to be operated. The operation is cumbersome and prone to errors, resulting in the failure of the connection and sealing of some gas inlets and outlets or liquid inlets and outlets, which in turn causes deviations in the experimental results.

[0056] Based on this, one embodiment of this application also provides an organ-on-a-chip fixture 10, which is used to seal the liquid inlet and outlet of the chip body 20 and connect the gas inlet and outlet of the chip body 20 to a pressure vacuum controller while clamping and fixing the organ chip, so as to facilitate experimental operation.

[0057] Specifically, see [link to relevant documentation] Figure 1 as well as Figure 2 One embodiment of the organ-on-a-chip fixture 10 includes a base 11 and a cover plate 12.

[0058] See Figure 5The base 11 is provided with a placement area for placing the chip body 20. The placement area has a first pneumatic interface 112 for communicating with the first gas inlet and outlet 231 of the chip body 20. The first pneumatic interface 112 is used to connect to a pneumatic vacuum controller (not shown).

[0059] See Figure 6 The cover plate 12 is connected to the base 11 and is used to abut against the side of the chip body 20 away from the base 11. The cover plate 12 is provided with a first sealing element 122 for sealing the liquid inlet and outlet of the chip body 20. The cover plate 12 is also provided with a second pneumatic interface 121 for communicating with the second gas inlet and outlet 211 of the chip body 20. The second pneumatic interface 121 is used to connect to a pneumatic vacuum controller.

[0060] In the aforementioned organ-on-a-chip fixture 10, a first pneumatic interface 112 is provided in the placement area of ​​the base 11. A second pneumatic interface 121 is provided in the cover plate 12, and the cover plate 12 is also provided with a first sealing element 122. Thus, by placing the chip body 20 on the placement area of ​​the base 11, and then connecting the cover plate 12 to the base 11 and abutting against the side of the chip body 20 away from the base 11, the first sealing element 122 can block the liquid inlet and outlet on the chip body 20, while the first pneumatic interface 112 is connected to the first gas inlet and outlet 231 of the chip body 20, and the second pneumatic interface 121 is connected to the second gas inlet and outlet 211 of the chip body 20. Thus, by connecting the first pneumatic interface 112 and the second pneumatic interface 121 to the pneumatic vacuum controller, the air pressure of the upper cavity 21 and the lower cavity 23 of the chip body 20 can be controlled, thereby creating a pressure difference on both sides of the porous membrane 24 containing the cell layer and causing deformation, thus simulating the respiratory movement of alveoli. Compared to traditional experimental procedures that require manually inserting and plugging each endotracheal tube, the organ-on-a-chip fixture 10 of this application eliminates the need to plug each of the numerous liquid inlets and outlets of the chip body 20 individually, as well as to connect each of the numerous gas inlets and outlets with endotracheal tubes. Simply connecting the first pneumatic interface 112 and the second pneumatic interface 121 to the pneumatic vacuum controller greatly simplifies the experimental procedure and reduces errors in experimental results caused by manually inserting endotracheal tubes or plugging them.

[0061] Furthermore, the organ-on-a-chip fixture 10 of this application has a first pneumatic interface 112 on the base 11 and a second pneumatic interface 121 on the cover plate 12. This can meet the needs of organ-on-a-chip devices that require pneumatic connectors to be connected on both sides, solving the problem that it is difficult to unify all pneumatic interfaces on the same side of the chip in complex multi-layer organ-on-a-chip structures. (Unifying all pneumatic interfaces on the same side of the chip requires forcibly passing the pneumatic interfaces through multiple layers of components to the other side of the organ-on-a-chip, which can easily cause air leakage and reduce the yield of organ-on-a-chip devices.)

[0062] See also Figure 5 In one embodiment, the placement area has a receiving groove 111 for accommodating the chip body 20, and a first pneumatic interface 112 is formed on the bottom wall of the receiving groove 111. By placing the chip body 20 in the receiving groove 111, the chip body 20 can be limited, preventing problems such as liquid inlet / outlet seal failure or gas inlet / outlet connection failure caused by displacement of the chip body 20 during assembly or experimentation. In addition, placing the chip body 20 in the receiving groove 111 can also effectively reduce the overall thickness of the organ-on-a-chip device.

[0063] See also Figure 5 In one embodiment, the placement area is further provided with an observation window 114 for observing the chip body 20. Exemplarily, the observation window 114 is located on the bottom wall of the receiving groove 111. Thus, the cells within the chip body 20 can be observed in real time during the experiment through the observation window 114, facilitating the recording of experimental results.

[0064] See Figure 1 as well as Figure 2 The organ-on-a-chip fixture 10 also includes a first pneumatic connector 30, which is connected to the first pneumatic interface 112. The first pneumatic interface 112 is connected to the pneumatic vacuum controller through the first pneumatic connector 30. Specifically, the first pneumatic connector 30 is used to connect to the air tube of the pneumatic vacuum controller, thus facilitating the connection between the first pneumatic interface 112 and the vacuum controller.

[0065] For example, the first pneumatic connector 30 can be a pagoda connector, which is easier to insert into the air tube so that the first pneumatic connector 30 can be connected to the pneumatic vacuum controller through the air tube. Understandably, in other embodiments, the first pneumatic connector 30 can also be other types of quick-connect connectors, which are not limited here.

[0066] See Figure 5 In one embodiment, the base 11 also has a first connection port 113 communicating with the first pneumatic interface 112, and the first pneumatic connector 30 is connected to the first connection port 113. Specifically, the first connection port 113 is provided with an internal thread, and the first pneumatic connector 30 is threadedly engaged with the first connection port 113, which facilitates the installation of the first pneumatic connector 30 onto the base 11.

[0067] See Figure 6In one embodiment, the cover plate 12 is provided with a plurality of first sealing elements 122, which are used to seal a plurality of liquid inlets and outlets on the chip body 20 in a one-to-one correspondence. For example, in one embodiment, the surface of the chip body 20 is provided with twelve liquid inlets and outlets (three first liquid inlets 212, three first liquid outlets 213, three second liquid inlets 221, and three second liquid outlets 222). Correspondingly, the cover plate 12 is provided with twelve first sealing elements 122, which seal each liquid inlet and outlet in a one-to-one correspondence, thereby preventing liquid leakage in the upper cavity 21 and middle cavity 22 of the chip body 20 during the experiment. Understandably, the number of first sealing elements 122 can be more or less, as long as it is the same as the number of liquid inlets and outlets of the chip body 20, and is not limited here.

[0068] For example, the first sealing element 122 can be a sealing ring. During sealing, the sealing ring surrounds the outer periphery of the liquid inlet and outlet and engages with the chip body 20 under pressure. Specifically, the pressure difference between the first sealing element 122 and the chip body 20 is 0.2 mm to 0.7 mm. The inner diameter of the first sealing element 122 is 1.5 to 3 times the diameter of the corresponding liquid inlet and outlet; the outer diameter of the first sealing element 122 is 1.2 to 1.5 times the inner diameter of the first sealing element 122.

[0069] Understandably, in other embodiments, the first seal 122 can also be a plug. When the cover plate 12 is pressed against the chip body 20, the plug is inserted into the liquid inlet and outlet, thereby sealing the liquid inlet and outlet, which can also prevent liquid leakage in the upper cavity 21 and middle cavity 22 of the chip body 20.

[0070] See Figure 6 In one embodiment, the cover plate 12 has multiple second pneumatic interfaces 121, which are used to communicate one-to-one with multiple second gas inlets and outlets 211 on the chip body 20. For example, in one embodiment, the surface of the chip body 20 is provided with three second gas inlets and outlets 211, and correspondingly, the cover plate 12 is provided with three second pneumatic interfaces 121, which are connected one-to-one with each other, thereby realizing pressure control of each upper cavity 21.

[0071] See Figure 2 as well as Figure 7In one embodiment, the organ-on-a-chip fixture 10 further includes a pneumatic connector 50. The pneumatic connector 50 has a pressure chamber 51 and a second connection port 52 communicating with the pressure chamber 51. The pneumatic connector 50 is connected to the cover plate 12, and the pressure chamber 51 is connected to all the second pneumatic interfaces 121. The second connection port 52 is used to connect to a pneumatic vacuum controller. Through the pneumatic connector 50, the pneumatic vacuum controller can be simultaneously connected to all the second pneumatic interfaces 121, thereby enabling simultaneous control of the air pressure in all upper chambers 21.

[0072] For example, in one embodiment, the pneumatic connector 50 and the cover plate 12 can be bonded together with double-sided tape or glue, thereby facilitating the assembly of the pneumatic connector 50 and the cover plate 12. In another embodiment, the pneumatic connector 50 and the cover plate 12 can also be an integrally formed structure.

[0073] See Figure 1 as well as Figure 2 The organ-on-a-chip fixture 10 also includes a second pneumatic connector 40, which is connected to a second connection port 52. The second connection port 52 is connected to a pneumatic vacuum controller via the second pneumatic connector 40. Specifically, the second pneumatic connector 40 is used to connect to the air tube of the pneumatic vacuum controller, thus facilitating the connection between the second pneumatic connector 40 and the vacuum controller.

[0074] For example, the second connection port 52 is provided with an internal thread, and the second pneumatic connector 40 is threadedly engaged with the second connection port 52, so that the second pneumatic connector 40 can be easily installed onto the pneumatic connector 50.

[0075] Furthermore, the second pneumatic connector 40 can be a pagoda connector, which is easier to insert into the air tube, so that the second pneumatic connector 40 can be connected to the pneumatic vacuum controller through the air tube. Understandably, in other embodiments, the second pneumatic connector 40 can also be other types of quick-connect connectors, which are not limited here.

[0076] See Figure 5 In one embodiment, the base 11 is provided with a first pneumatic sealing ring 115, which surrounds the periphery of the first pneumatic interface 112. The first pneumatic sealing ring 115 is used to seal the gap between the first pneumatic interface 112 and the first gas inlet / outlet 231, thereby preventing gas in the lower cavity 23 from leaking from the gap between the first pneumatic interface 112 and the first gas inlet / outlet 231.

[0077] For example, the first pneumatic sealing ring 115 can be a rubber sealing ring. During sealing, the first pneumatic sealing ring 115 surrounds the outer periphery of the first pneumatic interface 112 and the first gas inlet / outlet 231 and engages with the chip body 20 under pressure. Specifically, the pressure difference between the first pneumatic sealing ring 115 and the chip body 20 is 0.2 mm to 0.7 mm. The inner diameter of the first pneumatic sealing ring 115 is 1.5 to 3 times the diameter of the first gas inlet / outlet 231; the outer diameter of the first pneumatic sealing ring 115 is 1.2 to 1.5 times the inner diameter of the first pneumatic sealing ring 115.

[0078] See also Figure 5 In one embodiment, a gasket 116 is further provided on the bottom wall of the receiving groove 111 of the base 11, and the height of the gasket 116 protruding from the base 11 is equal to the height of the first pneumatic sealing ring 115 protruding from the base 11. This ensures that the chip body 20 remains horizontal after being placed in the receiving groove 111, preventing a decrease in sealing performance caused by tilting of the chip body 20. Preferably, the base 11 is provided with multiple gaskets 116, such as two, three, four, or more, which are spaced apart on the bottom wall of the receiving groove 111, thereby further improving the horizontal placement of the chip body 20.

[0079] See Figure 6 In one embodiment, the cover plate 12 is provided with a second pneumatic sealing ring 123, which surrounds the periphery of the second pneumatic interface 121. The second pneumatic sealing ring 123 is used to seal the gap between the second pneumatic interface 121 and the second gas inlet / outlet 211, thereby preventing gas in the upper cavity 21 from leaking from the gap between the second pneumatic interface 121 and the second gas inlet / outlet 211.

[0080] Furthermore, there are multiple second pneumatic sealing rings 123, and each second pneumatic sealing ring 123 is set in a one-to-one correspondence with a second pneumatic interface 121, thus ensuring the sealing between each second pneumatic interface 121 and the corresponding second gas inlet / outlet 211.

[0081] For example, the second pneumatic sealing ring 123 can be a rubber sealing ring. During sealing, the second pneumatic sealing ring 123 surrounds the outer periphery of the second pneumatic interface 121 and the second gas inlet / outlet 211 and engages with the chip body 20 under pressure. Specifically, the pressure difference between the second pneumatic sealing ring 123 and the chip body 20 is 0.2 mm to 0.7 mm. The inner diameter of the second pneumatic sealing ring 123 is 1.5 to 3 times the diameter of the second gas inlet / outlet 211; the outer diameter of the second pneumatic sealing ring 123 is 1.2 to 1.5 times the inner diameter of the second pneumatic sealing ring 123.

[0082] See Figure 5 as well as Figure 6In one embodiment, the base 11 is provided with a positioning post 117, and the positioning post 117 has a threaded hole 118. The cover plate 12 has a positioning countersunk hole 124, and a connecting hole 125 is formed through the positioning countersunk hole 124. The positioning post 117 is inserted into the positioning countersunk hole 124, and the threaded hole 118 is aligned with the connecting hole 125. Figure 1 The organ-on-a-chip fixture 10 also includes a threaded connector 60, which passes through the connection hole 125 and is threadedly engaged with the threaded hole 118.

[0083] By inserting the positioning pin 117 into the positioning countersunk hole 124, the base 11 and the cover plate 12 can be initially positioned before being connected and fixed, ensuring that the second pneumatic interface 121 on the cover plate 12 is aligned with the second gas inlet / outlet 211 on the chip body 20, and that the first sealing element 122 is aligned with the liquid inlet / outlet. The base 11 and the cover plate 12 are connected by the threaded connector 60, making the assembly of the base 11 and the cover plate 12 more convenient.

[0084] Understandably, in other embodiments, the positioning post 117 may also be disposed on the cover plate 12, and the positioning countersunk hole 124 may be formed on the base 11.

[0085] In other embodiments, the base 11 and the cover plate 12 may also be fixed by a combination of nuts and bolts.

[0086] Exemplarily, in one embodiment, the method of using the above-described organ-on-a-chip device is as follows:

[0087] Before use, first connect the second pneumatic connector 40 to the pneumatic connector 50, then glue the pneumatic connector 50 to the cover plate 12, and then connect the first pneumatic connector 30 to the base 11.

[0088] Cells are then seeded into the porous membrane 24 of the chip body 20, and the cell suspension is perfused into the upper cavity 21 and the middle cavity 22 through the liquid inlet and outlet of the chip structure. Then, by reversing the chip body 20, gravity is used to seed the cells on both sides of the porous membrane 24 to form a cell layer.

[0089] After the cells are completely adhered to the porous membrane 24, the chip body 20 is placed in the receiving groove 111 of the base 11, the first gas inlet and outlet 231 is aligned with the first pneumatic sealing ring 115, and then the cover plate 12 is placed on the chip body 20, the positioning countersunk hole 124 is aligned with the positioning post 117 of the base 11, and the cover plate 12 is locked on the base 11 by the threaded connector 60 and the positioning post 117.

[0090] Finally, the first pneumatic connector 30 and the second pneumatic connector 40 are connected to the pneumatic vacuum controller through the trachea. By adjusting the pneumatic pressure or vacuum cycle output of the pneumatic vacuum controller, a pressure difference is formed on both sides of the porous membrane 24 containing the cell layer, causing deformation and simulating the respiratory movement of alveoli. The cells inside the chip body 20 can be observed in real time through the imaging window.

[0091] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0092] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

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