Organ chip

Abstract

The organ chip comprises a main body and micro columns, a first cavity, a second cavity located below the first cavity and communicated with the first cavity, a liquid inlet communicating port communicated with the first cavity and a liquid outlet communicating port communicated with the first cavity are formed in the main body, and the main body is provided with a step surface located between the first cavity and the second cavity and facing the first cavity; the step surface comprises a first area and a second area connected with the first area; the microcolumn is located in the first cavity, is connected with the first area and protrudes out of the first area, and the second area is a blank area. According to the organ chip, the cavity and the micro-column, fluid entering from the liquid inlet communication port passes through the micro-column in the process of flowing to the liquid outlet communication port, so that stable and independent culture of a biological model in the second cavity and sufficient liquid exchange are realized.

Description

Technical Field

[0001] The present application relates to the technical field of organ chips, and in particular to an organ chip. Background Art

[0002] Currently, three-dimensional biological models, such as various organ models and organoids, have been widely used to replicate the complex structure and function of human organs in vitro, provide accurate models for disease research and drug testing, customize disease models for patients, realize the development of personalized diagnosis and treatment plans, and accelerate drug screening and safety assessment.

[0003] However, there are still many problems. For example, the in vitro organ model cultured under long-term shock is different from the actual working state, and the growth process of the in vitro organ model under extreme conditions cannot be simulated. Summary of the invention

[0004] The present application provides an organ chip for culturing a three-dimensional biological model / organ model in vitro under special environmental conditions to reduce the impact of special conditions on its growth state. For example, it is applied to the cultivation of a three-dimensional biological model / organ model under extremely special conditions such as overweight, weightlessness, and severe shock.

[0005] The present application embodiment provides an organ chip, comprising:

[0006] The main body is formed with a first cavity, a second cavity located below the first cavity and connected to the first cavity, a liquid inlet communication port and a liquid outlet communication port connected to the first cavity and spaced from each other, and the main body has a step surface located between the first cavity and the second cavity and facing the first cavity, and the step surface includes a first area and a second area connected to the first area;

[0007] The micro-column is located in the first cavity, the micro-column is connected to the first area and protrudes from the first area, and the second area is a blank area.

[0008] In some embodiments, the second cavity has two third side walls disposed opposite to each other along a first direction, and the first direction is perpendicular to the thickness direction of the body;

[0009] Each third side wall is correspondingly provided with at least one first area, and each first area is connected to a micro-column.

[0010] In some of the embodiments, each third sidewall is correspondingly provided with a plurality of first regions, and the plurality of first regions are spaced apart along an extension direction of the third sidewall.

[0011] In some embodiments, the main body is formed with a plurality of second cavities located below the first cavity and connected to the first cavity, the plurality of second cavities are arranged along the first direction, and each second cavity has two third side walls arranged opposite to each other along the first direction.

[0012] In some embodiments, along the first direction, the liquid inlet communication port and the liquid outlet communication port are located on opposite sides of the first cavity.

[0013] In some embodiments, the main body is formed with a liquid inlet cavity communicated with the first cavity, and the liquid inlet cavity is provided with a liquid inlet communication port.

[0014] In some embodiments, the main body is formed with a liquid outlet cavity communicated with the first cavity, and the liquid outlet cavity is provided with a liquid outlet communication port.

[0015] In some of these embodiments, the second zone connects the entire circumference of the first zone.

[0016] In some embodiments, the main body is formed with multiple first cavities, second cavities corresponding to each first cavity, a liquid inlet connection port and a liquid outlet connection port; the multiple first cavities are arranged along the second direction, and the second direction is perpendicular to the thickness direction of the main body.

[0017] In some embodiments, the main body is further formed with a communication channel located between two adjacent first cavities, and the communication channel connects the liquid outlet communication port corresponding to one of the two adjacent first cavities with the liquid inlet communication port corresponding to the other first cavity.

[0018] In some embodiments, the subject comprises:

[0019] Base plate;

[0020] The middle plate, the bottom plate is arranged below the middle plate and a second cavity is formed therebetween; and

[0021] The cover plate is arranged above the middle plate and a first cavity is formed between the two.

[0022] In some embodiments, an upper groove is provided on the upper surface of the middle plate, and a first cavity is formed between an inner wall of the upper groove and a lower surface of the cover plate.

[0023] In some of the embodiments, a lower groove is provided on the lower surface of the middle plate, and a second cavity is formed between an inner wall of the lower groove and an upper surface of the bottom plate.

[0024] In some of the embodiments, the main body is further formed with a liquid inlet channel and a liquid outlet channel, the liquid inlet channel is connected to the liquid inlet connecting port, and the liquid outlet channel is connected to the liquid outlet connecting port; wherein the liquid inlet channel and the liquid outlet channel are located on the same side of the first cavity; and / or, at least a portion of the liquid inlet channel is bent; and / or, the organ chip also includes a bubble removal member connected to the liquid inlet channel.

[0025] In some embodiments, the main body is further formed with a liquid inlet channel and a liquid outlet channel, the liquid inlet channel is connected to the liquid inlet communication port, and the liquid outlet channel is connected to the liquid outlet communication port;

[0026] Among them, the organ chip also includes a liquid inlet pipeline, which includes a liquid inlet pipe and a liquid inlet filter, and a liquid inlet port connected to the liquid inlet channel is formed on the surface of the main body, and the liquid inlet pipe connects the liquid inlet port and the liquid inlet filter; and / or, the organ chip also includes a liquid outlet pipeline, which includes a liquid outlet pipe and a liquid outlet filter, and a liquid outlet port connected to the liquid outlet channel is formed on the surface of the main body, and the liquid outlet pipe connects the liquid outlet port and the liquid outlet filter.

[0027] In the organ chip of the embodiment of the present application, the second cavity is designed to be located below the first cavity, and the liquid inlet connecting port and the liquid outlet connecting port are both connected to the first cavity. Therefore, the fluid (such as culture medium) entering through the liquid inlet connecting port will first enter the first cavity, and then flow from the first cavity into the second cavity below it and the liquid outlet connecting port.

[0028] The organ chip of the embodiment of the present application, through the design of the chamber and microcolumns, can achieve stable and independent cultivation of the biological model in the second chamber and sufficient liquid exchange under extremely special conditions such as overweight, weightlessness, and severe vibration.

[0029] In the present application, the biological model is constrained by the chamber and the micro-columns, so that the position of the biological model is fully fixed.

[0030] In the present application, the fluid flows into the second cavity through the microcolumn, which can maintain the circulation of the fluid to the greatest extent possible, while ensuring the exchange of culture medium and metabolites; at the same time, the design of the microcolumn further prevents the accumulation and blockage of foreign matter in the fluid and prevents multiple in vitro organs from aggregating and adhering to cause necrosis. The suspended matter in the fluid entering through the liquid inlet connection port will be at least partially adsorbed on the microcolumn in the process of flowing to the liquid outlet connection port, thereby improving the problem of the suspended matter accumulating at the liquid outlet connection port and causing blockage of the liquid outlet connection port. The above-mentioned design step surface also includes a second area connected to the first area, and the second area is a blank area, so that the fluid can pass through the blank area, that is, pass near the microcolumn, which is conducive to the adsorption of suspended matter in the fluid on the microcolumn, thereby improving the adsorption effect of the suspended matter.

[0031] In the present application, the connection design between the first chamber and the second chamber and the connecting channel design can make the liquid replacement more thorough during the cultivation process of the biological model, and further enhance the interaction between the culture medium and biological metabolites. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0033] Figure 1is a schematic diagram of the structure of the organ chip provided in some embodiments of the present application;

[0034] Figure 2 yes Figure 1 A schematic diagram of the exploded structure of the organ chip is shown;

[0035] Figure 3 yes Figure 1 A schematic diagram of the structure of the middle plate in the organ chip is shown;

[0036] Figure 4 yes Figure 1 A partial perspective structural schematic diagram of an organ chip is shown;

[0037] Figure 5 yes Figure 4 Schematic diagram of the cross-sectional structure along the AA direction.

[0038] Description of reference numerals:

[0039] 1. Organ Chips;

[0040] 10. Main body; 11. First cavity; 111. First side wall; 112. Second side wall; 12. Second cavity; 121. Third side wall; 13. Liquid inlet channel; 131. Liquid inlet communication port; 132. Liquid inlet port; 133. Liquid inlet cavity; 14. Liquid outlet channel; 141. Liquid outlet communication port; 142. Liquid outlet port; 143. Liquid storage cavity; 15. Step surface; 151. First area; 152. Second area; 16. Bottom plate; 17. Middle plate; 171. Upper groove; 172. Lower groove; 18. Cover plate;

[0041] 20. Microcolumns;

[0042] 30. Liquid inlet pipeline; 31. Liquid inlet pipe; 32. Liquid inlet filter; 33. Luer female connector; 34. Luer male connector;

[0043] 40. liquid outlet pipeline; 41. liquid outlet pipe; 42. liquid outlet filter; 43. Luer female connector; 44. Luer male connector;

[0044] 50. Remove air bubble parts;

[0045] x, first direction; y, second direction; z, thickness direction. DETAILED DESCRIPTION

[0046] In order to make the objectives, technical solutions and advantages of the present application more clear, the embodiments of the present application will be further described in detail below with reference to the accompanying drawings.

[0047] When the following description refers to the drawings, unless otherwise indicated, the same numbers in different drawings represent the same or similar elements. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present application. Instead, they are only examples of devices and methods consistent with some aspects of the present application as detailed in the attached claims.

[0048] See also Figures 1 to 5 An embodiment of the present application provides an organ chip 1 , which includes a main body 10 and a microcolumn 20 .

[0049] The main body 10 is formed with a first cavity 11, a second cavity 12 located below the first cavity 11 and connected to the first cavity 11, a liquid inlet communication port 131 and a liquid outlet communication port 141 connected to the first cavity 11 and spaced apart from each other, and the main body 10 has a step surface 15 located between the first cavity 11 and the second cavity 12 and facing the first cavity 11, and the step surface 15 includes a first area 151 and a second area 152 connected to the first area 151. The microcolumn 20 is located in the first cavity 11, the microcolumn 20 is connected to the first area 151 and protrudes from the first area 151, and the second area 152 is a blank area.

[0050] The above-mentioned second chamber 12 is located below the first chamber 11, and the liquid inlet connecting port 131 and the liquid outlet connecting port 141 are both connected to the first chamber 11. The fluid (such as culture fluid) entering through the liquid inlet connecting port 131 will first enter the first chamber 11, and then flow from the first chamber 11 into the second chamber 12 and the liquid outlet connecting port 141 below it.

[0051] Through the design of the first cavity 11, the second cavity 12 and the microcolumn 20, the biological model in the second cavity 12 is constrained to achieve a fully fixed position of the biological model. The fluid flows into the second cavity 12 through the microcolumn 20, which can maintain the circulation of the fluid to the greatest extent possible, while ensuring the exchange of the culture medium and metabolites; in addition, the suspended matter in the fluid entering through the liquid inlet connection port 131 will be at least partially adsorbed on the microcolumn 20 in the first cavity 11 during the process of flowing to the liquid outlet connection port 141, which can improve the problem of the suspended matter gathering at the liquid outlet connection port 141 and causing the liquid outlet connection port 141 to be blocked.

[0052] The designed step surface 15 also includes a second area 152 connected to the first area 151. The second area 152 is a blank area, so that the fluid can pass through the blank area, that is, pass near the microcolumn 20, which is beneficial for the suspended matter in the fluid to be adsorbed on the microcolumn 20, thereby improving the adsorption effect of the suspended matter.

[0053] The second area 152 may be connected to one side of the first area 151, or may be connected to at least two sides of the first area 151. If the second area 152 is connected to one side of the first area 151, the fluid may pass through one side of the first area 151, so that the microcolumns 20 can adsorb suspended matter in the fluid on this side. If the second area 152 is connected to at least two sides of the first area 151, the fluid may pass through at least two sides of the first area 151, so that the microcolumns 20 can adsorb suspended matter in the fluid on these at least two sides, thereby improving the adsorption effect on the suspended matter.

[0054] In the embodiment of the present application, the second area 152 is connected to the entire circumference of the first area 151, that is, the first area 151 is completely wrapped by the second area 152, so that the fluid can pass through the entire circumference of the first area 151, and the entire circumference of the microcolumn 20 can be in contact with the fluid.

[0055] With respect to the main body 10, in an exemplary solution, the second cavity 12 has two third side walls 121 arranged opposite to each other along the first direction x, the first direction x is perpendicular to the thickness direction z of the main body 10, each third side wall 121 is correspondingly provided with at least one first area 151, and each first area 151 is connected to a microcolumn 20. Thus, when the fluid flows along the first direction x, the design of the first cavity 11, the second cavity 12 and the microcolumn 20 can achieve better fluid circulation, ensure the exchange of culture medium and metabolites, and achieve better adsorption of suspended matter and fixation of biological models.

[0056] In another exemplary embodiment, each side wall of the second cavity 12 (for example, the third side wall 121 and the side wall oppositely arranged along the second direction y) is correspondingly provided with at least one first area 151, and the microcolumns 20 are connected to the first areas 151 one by one and protrude from the first areas 151, so that the microcolumns 20 are arranged all around the top of the second cavity 12. On the one hand, multiple microcolumns 20 can realize the circulation and exchange of fluids from multiple directions and the adsorption of suspended matter, thereby improving the adsorption effect of suspended matter. On the other hand, multiple microcolumns 20 can confine the in vitro organs within the second cavity 12 to fix the position of the biological model.

[0057] The side wall of the second cavity 12 (for example, the third side wall 121 or each side wall) is correspondingly provided with at least one first area 151, which can be: Figure 4 , the side wall of the second cavity 12 (for example, the third side wall 121 or each side wall) is correspondingly provided with a plurality of first areas 151. The number of first areas 151 corresponding to each side wall may be equal or unequal, and the present application does not limit this. If the side wall of the second cavity 12 (for example, the third side wall 121 or each side wall) is correspondingly provided with a plurality of first areas 151, the plurality of first areas 151 may be arranged at intervals along the extension direction of the corresponding side wall, so as to achieve a better effect of fixing the extracorporeal organ in the second cavity 12.

[0058] See also Figure 4 and Figure 3 The main body 10 is formed with a plurality of second cavities 12 located below the first cavity 11 and connected to the first cavity 11. Each second cavity 12 can be used to place an in vitro organ, so that the organ chip 1 can simultaneously culture multiple in vitro organs.

[0059] The multiple second cavities 12 connected to the first cavity 11 can be arranged randomly, or arranged along the first direction x or the second direction y, and the first direction x and the second direction y are perpendicular to the thickness direction z of the body 10. In the embodiment of the present application, the multiple second cavities 12 connected to the first cavity 11 are arranged along the first direction x. The positions of the first direction x and the second direction y can be switched, and there is no limitation on this.

[0060] The first cavity 11 has two first side walls 111 arranged opposite to each other along the first direction x. The above-mentioned design of arranging the multiple second cavities 12 connected to the first cavity 11 along the first direction x can realize the regular arrangement of the multiple second cavities 12 below the first cavity 11, which is conducive to the culture fluid entering through the first cavity 11 to reach each second cavity 12 below, and is conducive to the regular structural design of each second cavity 12 connected to the first cavity 11. For example, Figure 4 In the embodiment, each second cavity 12 connected to the first cavity 11 has two third side walls 121 arranged opposite to each other along the first direction x, and the third side walls 121 may be parallel to the first side wall 111. Further, the first cavity 11 has two second side walls 112 arranged opposite to each other along the second direction y, and each first side wall 111 is connected between two second side walls 112. Each second cavity 12 may include four side walls, and two of the side walls are the third side walls 121 arranged opposite to each other along the first direction x, and the other two side walls are arranged opposite to each other along the second direction y and may be parallel to the second side walls 112.

[0061] Furthermore, each third side wall 121 of each second cavity 12 is correspondingly provided with at least one first area 151, and each first area 151 is connected to a microcolumn 20. In this way, the microcolumn 20 can limit the biological model in the corresponding second cavity 12 while ensuring the flow of fluid, and prevent multiple in vitro organs from aggregating and adhering to cause necrosis. Among them, the second cavity 12 can be treated with anti-adhesion, for example, soaked in an anti-adhesion rinsing solution for 10 minutes, so as to realize the 3D growth of in vitro biological models, such as organoids, without the need for shaking conditions.

[0062] The multiple second chambers 12 connected to the above-mentioned first chamber 11 are arranged along the first direction x, and each third side wall 121 of each of the above-mentioned second chambers 12 is correspondingly provided with at least one first area 151, and each first area 151 is connected to a microcolumn 20, so that when the fluid flows from one second chamber 12 to another second chamber 12, that is, when the fluid flows along the first direction x, the microcolumns 20 arranged at each first area 151 and the connection method of the second chamber 12 can make the liquid replacement of the biological model in the second chamber 12 more thorough, thereby enhancing the interaction between the culture medium and the biological metabolites.

[0063] It can be understood that the plurality of second cavities 12 connected to the first cavity 11 are arranged along the first direction x, and at least one first area 151 can be correspondingly provided on the side wall of each second cavity 12, and each first area 151 is connected to a micro-pillar 20. That is, the micro-pillars 20 are provided all around the top of each second cavity 12, so that the adsorption of suspended matter can be achieved from multiple directions, the adsorption effect of suspended matter can be improved, and the restraint effect on the external organs can be improved.

[0064] It is understandable that the first areas 151 corresponding to the two third side walls 121 of two adjacent second cavities 12 may be shared or separately arranged. Figure 4 The first areas 151 corresponding to the two third side walls 121 of two adjacent second cavities 12 are shared, so that the structural design of the organ chip 1 is more compact. More second cavities 12 can be set in the same size to achieve the culture of more in vitro organs.

[0065] The liquid inlet communication port 131 and the liquid outlet communication port 141 connected to the first cavity 11 can be located on opposite sides of the first cavity 11 along the first direction x. When the fluid flows, it generally flows from the liquid inlet communication port 131 toward the liquid outlet communication port 141, that is, it generally flows along the first direction x. In this way, the two third side walls 121 of the second cavity 12 designed to be relatively arranged along the first direction x are each correspondingly provided with at least one first area 151, and each first area 151 is connected to a microcolumn 20, so that each microcolumn 20 can better maintain the full circulation of the fluid during the flow of the fluid, and at the same time achieve the independent culture effect of the in vitro organ model in the second cavity 12. In addition, the multiple second cavities 12 connected to the first cavity 11 are arranged along the first direction x, so that the flow direction of the fluid is roughly the same as the arrangement direction of the multiple second cavities 12.

[0066] In an exemplary solution, the liquid inlet communication port 131 can be disposed on a first side wall 111 of the first cavity 11 or on the step surface 15. If the liquid inlet communication port 131 is disposed on the step surface 15, since the fluid enters the first cavity 11 through the liquid inlet communication port 131, disposing the liquid inlet communication port 131 on the step surface 15 at the bottom of the first cavity 11 is conducive to the fluid entering the first cavity 11 being at a low position, and being able to flow toward the second cavity 12 below the step surface 15 in a timely and efficient manner. In another exemplary solution, see Figure 4 The main body 10 is formed with a liquid inlet cavity 133 connected with the first cavity 11, and the liquid inlet cavity 133 is provided with a liquid inlet communication port 131. That is, the first cavity 11 and the liquid inlet communication port 131 are connected via the liquid inlet cavity 133, wherein the liquid inlet cavity 133 can store a certain amount of fluid, and can ensure the smoothness of the supply of fluid into the first cavity 11. The liquid inlet communication port 131 can be arranged on the bottom wall of the liquid inlet cavity 133, which is not limited. The depth of the liquid inlet cavity 133 can be greater than the depth of the first cavity 11, which is not limited.

[0067] In an exemplary solution, the liquid outlet communication port 141 can be disposed on the other first side wall 111 of the first cavity 11 or on the step surface 15. If the liquid outlet communication port 141 is disposed on the step surface 15, since the fluid is discharged from the first cavity 11 through the liquid outlet communication port 141, disposing the liquid outlet communication port 141 on the step surface 15 at the bottom of the first cavity 11 is conducive to the liquid outlet communication port 141 being at a low position in the first cavity 11, so that the fluid in the first cavity 11 can be discharged in a timely and efficient manner. In another exemplary solution, see Figure 4 The main body 10 is formed with a liquid outlet cavity 143 connected to the first cavity 11, and the liquid outlet cavity 143 is provided with a liquid outlet communication port 141. That is, the first cavity 11 is connected with the liquid outlet communication port 141 via the liquid outlet cavity 143, wherein the liquid outlet cavity 143 can store a certain amount of fluid, so that the discharge at the liquid outlet communication port 141 can be smoother. The liquid outlet communication port 141 can be arranged on the bottom wall of the liquid outlet cavity 143, which is not limited. The depth of the liquid outlet cavity 143 can be greater than the depth of the first cavity 11, which is not limited.

[0068] The first side wall 111 and the second side walls 112 are arranged at their junctions. It can be understood that the liquid inlet communication port 131 and the liquid outlet communication port 141 are arranged corresponding to two adjacent corners of the first cavity 11, respectively, so that the liquid inlet communication port 131 and the liquid outlet communication port 141 can be separated as much as possible, which is conducive to the fluid entering through the liquid inlet communication port 131 to reach the second cavity 12 and then flow out through the liquid outlet communication port 141.

[0069] It should be noted that the liquid inlet communication port 131 and the liquid outlet communication port 141 may also be respectively disposed at two opposite corners of the first cavity 11 to meet different usage requirements, which is not limited in the embodiment of the present application.

[0070] See also Figure 4 and Figure 3 The main body 10 is formed with a plurality of first cavities 11, a second cavity 12 corresponding to each first cavity 11, a liquid inlet communication port 131 and a liquid outlet communication port 141, and the plurality of first cavities 11 are arranged along the second direction y. In this way, the number of second cavities 12 included in the organ chip 1 can be increased, and the number of in vitro organs that can be cultured simultaneously by the organ chip 1 can be increased.

[0071] The above-mentioned design and the second cavity 12, the liquid inlet connecting port 131 and the liquid outlet connecting port 141 corresponding to each first cavity 11 can make the flow of the fluid in each cavity 11 independent of each other, and the second cavity 12 corresponding to different first cavities 11 has better independence, so that the in vitro organs cultured therein are not easy to aggregate, adhere and cause necrosis.

[0072] Further, see Figure 4 The main body 10 is also formed with a connecting channel 19 located between two adjacent first cavities 11, and the connecting channel 19 connects the liquid outlet connecting port 141 corresponding to one of the two adjacent first cavities 11 with the liquid inlet connecting port 131 corresponding to the other first cavity 11. In this way, the serial connection of multiple first cavities 11 can be achieved, which is conducive to simplifying the liquid inlet and outlet operations of the organ chip 1, and the liquid replacement is more thorough. For example, Figure 4 In the embodiment, the main body 10 is formed with three first chambers 11 arranged along the second direction y, and the liquid outlet communication port 141 of the first first chamber 11 can be connected with the liquid inlet communication port 131 of the second first chamber 11 via the communication channel 19, and the liquid outlet communication port 141 of the second first chamber 11 can be connected with the liquid inlet communication port 131 of the third first chamber 11 via the communication channel 19, so that the entire organ chip 1 only needs to take in liquid through the liquid inlet communication port 131 of the first first chamber 11 and discharge liquid through the liquid outlet communication port 141 of the third first chamber 11, and the liquid replacement is more thorough.

[0073] In some embodiments, see Figure 4The main body 10 is also formed with a liquid inlet channel 13, and the liquid inlet channel 13 is connected to the first cavity 11 at a liquid inlet connecting port 131. The surface of the main body 10 is formed with a liquid inlet port 132 connected to the liquid inlet channel 13. In this way, it is beneficial to allow the fluid to pass from the surface of the main body 10 into the liquid inlet channel 13 so that the fluid enters the first cavity 11 in the main body 10, and compared with the related art that requires opening the cover to add liquid, the sealing is better. It should be noted that if the main body 10 is formed with a plurality of first cavities 11 and a connecting channel 19 located between two adjacent first cavities 11, the liquid inlet channel 13 can be connected to the liquid inlet connecting port 131 corresponding to a first cavity 11 located on one side edge, for example, Figure 4 In the embodiment, the liquid inlet channel 13 is communicated with the liquid inlet communication port 131 corresponding to the first first chamber 11 .

[0074] In some embodiments, at least a portion of the liquid inlet channel 13 is curved. Designing at least a portion of the liquid inlet channel 13 to be curved is conducive to extending the liquid inlet channel 13 and extending the path for the fluid to enter the first chamber 11. The longer the path for the fluid to enter the first chamber 11, the better the bubble removal effect. For example, see Figure 4 The liquid inlet channel 13 may include an inner ring section and two half outer ring sections arranged on the periphery of the inner ring section and connected to the inner ring section. The fluid in the liquid inlet channel 13 may flow through half of the outer ring section, the inner ring section and the other half of the outer ring section in sequence, thereby extending the path for the fluid to enter the first cavity 11 and improving the bubble removal effect.

[0075] In some embodiments, the organ chip 1 further includes a degassing member 50 connected to the liquid inlet channel 13. The degassing member 50 can be directly selected from the degassing members in the related art, which will not be described in detail.

[0076] In some embodiments, the main body 10 is further formed with a liquid outlet channel 14, the liquid outlet channel 14 is connected to the first cavity 11 at a liquid outlet communication port 141, and a liquid outlet port 142 connected to the liquid outlet channel 14 is formed on the surface of the main body 10. In this way, it is beneficial to discharge the fluid from the surface of the main body 10. It should be noted that if the main body 10 is formed with a plurality of first cavities 11 and a communication channel 19 located between two adjacent first cavities 11, the liquid outlet channel 14 can be connected to the liquid outlet communication port 141 corresponding to a first cavity 11 located at the other side edge, for example, Figure 4 In the embodiment, the liquid outlet channel 14 is communicated with the liquid outlet communication port 141 corresponding to the third first cavity 11 .

[0077] The liquid outlet channel 14 and the liquid inlet channel 13 are independent of each other, so that the channels for the fluid to enter and exit the first cavity 11 are independent of each other and will not cause interference. Figure 4The liquid outlet channel 14 may include a short ring segment, which may be located below the inner ring segment and the two semi-outer ring segments of the liquid inlet channel 13 so as to be independent of the inner ring segment and the two semi-outer ring segments of the liquid inlet channel 13 .

[0078] In some embodiments, the liquid inlet channel 13 and the liquid outlet channel 14 may be located on the same side of the first cavity 11, so that the arrangement of the liquid inlet channel 13 and the liquid outlet channel 14 will not interfere with the first cavity 11 and the second cavity 12. Figure 4 , the liquid inlet channel 13 and the liquid outlet channel 14 are both located on the side where one of the first side walls 111 of the first cavity 11 is located; that is, the liquid inlet channel 13 and the liquid outlet channel 14 are both located on the right side / left side of the first cavity 11. Of course, the liquid inlet channel 13 and the liquid outlet channel 14 can also be located on the side where one of the second side walls 112 of the first cavity 11 is located; that is, the liquid inlet channel 13 and the liquid outlet channel 14 are both located on the front side / rear side of the first cavity 11, which is not limited to this.

[0079] In some embodiments, the inlet port 132 of the inlet channel 13 and the outlet port 142 of the outlet channel 14 can be located on the same side of the body 10, so as to achieve the inflow and outflow of the first cavity 11 on the same side of the organ chip 1. Figure 4 , the liquid inlet port 132 of the liquid inlet channel 13 and the liquid outlet port 142 of the liquid outlet channel 14 are both located on the right side of the main body 10 (for example, the right side wall or the right end face of the main body 10). Of course, the liquid inlet port 132 of the liquid inlet channel 13 and the liquid outlet port 142 of the liquid outlet channel 14 can also be located on the left side of the main body 10 (for example, the left side wall or the left end face of the main body 10), the front side (for example, the front side wall or the front end face of the main body 10), or the rear side (for example, the rear side wall or the rear end face of the main body 10).

[0080] See also Figure 5 The main body 10 includes a bottom plate 16, a middle plate 17 and a cover plate 18. The bottom plate 16 is disposed below the middle plate 17, and the second cavity 12 is formed therebetween. The cover plate 18 is disposed above the middle plate 17, and the first cavity 11 is formed therebetween. By splitting the main body 10 into the bottom plate 16, the middle plate 17 and the cover plate 18, the second cavity 12 and the first cavity 11 can be easily processed and formed.

[0081] The bottom plate 16 and the middle plate 17 may be connected by gluing or the like, and the cover plate 18 and the middle plate 17 may be connected by gluing or the like, without limitation. Medical grade pressure-sensitive adhesive with high biocompatibility may be used for gluing, without limitation.

[0082] In some embodiments, the lower surface of the middle plate 17 is provided with a lower groove 172, and the second cavity 12 is formed between the inner wall of the lower groove 172 and the upper surface of the bottom plate 16. That is, only by providing a groove on the middle plate 17, the second cavity 12 can be formed when the middle plate 17 is connected to the bottom plate 16, which can simplify the processing technology. In other embodiments, it is also possible to choose to provide a groove on the upper surface of the bottom plate 16, or to provide a groove on both the upper surface of the bottom plate 16 and the lower surface of the middle plate 17 to form the second cavity 12, which is not limited.

[0083] In some embodiments, see Figure 5 The bottom plate 16 can be arranged corresponding to the second cavity 12 and the liquid inlet channel 13 and the liquid outlet channel 14; that is, the bottom plate 16 is approximately Figure 5 The second cavity 12 on the left side of the middle plate 17 extends to the liquid inlet channel 13 and the liquid outlet channel 14 on the right side thereof. At this time, the portion of the bottom plate 16 corresponding to the liquid inlet channel 13 and the liquid outlet channel 14 (that is, the right side of the bottom plate 16) can form at least part of the liquid inlet channel 13 and / or at least part of the liquid outlet channel 14 with the middle plate 17. In other embodiments, the bottom plate 16 can also be only provided corresponding to the second cavity 12; that is, the bottom plate 16 is approximately located at Figure 5 The left side of the middle plate 17.

[0084] In some embodiments, an upper groove 171 is provided on the upper surface of the middle plate 17, and a first cavity 11 is formed between the inner wall of the upper groove 171 and the lower surface of the cover plate 18. That is, only by providing a groove on the middle plate 17, the first cavity 11 can be formed when the middle plate 17 and the cover plate 18 are connected, which can simplify the processing technology. In other embodiments, a groove can be provided on the lower surface of the cover plate 18, or a groove can be provided on both the lower surface of the cover plate 18 and the upper surface of the middle plate 17 to form the first cavity 11, which is not limited to this.

[0085] In some embodiments, see Figure 5 , the cover plate 18 can be arranged only corresponding to the first cavity 11; that is, the cover plate 18 is approximately located Figure 5 In other embodiments, the cover plate 18 may also be arranged corresponding to the first cavity 11 and the liquid inlet channel 13 and the liquid outlet channel 14; that is, the cover plate 18 is approximately Figure 5 The first cavity 11 on the left side of the middle plate 17 extends to the liquid inlet channel 13 and the liquid outlet channel 14 on the right side thereof. In the embodiment of the present application, the cover plate 18 is only provided corresponding to the first cavity 11; that is, the cover plate 18 is approximately located at Figure 5 The left side of the middle plate 17 is provided so that the right side of the middle plate 17 can be provided with a degassing member 50 which is connected with the liquid inlet channel 13 .

[0086] The microcolumn 20 may have any shape. For example, the cross section of the microcolumn 20 may be roughly circular, square, etc., without limitation. The cross section of the microcolumn 20 may remain unchanged or may vary along the extension direction of the microcolumn 20; for example, the cross section of the microcolumn 20 may gradually increase, gradually decrease, or partially increase and partially decrease in the direction from one end of the microcolumn 20 connected to the first region 151 to the other end, without limitation.

[0087] In some embodiments, the microcolumn 20 may be a first microcolumn, and the height of the first microcolumn is less than the height of the first cavity 11. Designing the height of the first microcolumn to be less than the height of the first cavity 11 can reduce the obstruction of the first microcolumn to the flow rate of the fluid and improve the fluid replacement efficiency of the organ chip 1.

[0088] In some embodiments, the microcolumn 20 may be a second microcolumn, and the height of the second microcolumn is equal to the height of the first cavity 11. In this way, the second microcolumn can not only achieve sufficient circulation and liquid interaction of the fluid as described above, and achieve independent culture of the in vitro organ model in the second cavity 12, but also support the cover plate 18, thereby improving the structural strength of the organ chip 1.

[0089] It can be understood that the plurality of micro-pillars 20 in the embodiment of the present application may all be first micro-pillars, may all be second micro-pillars, or may partly be first micro-pillars and partly be second micro-pillars, and this is not limited.

[0090] In some embodiments, see Figure 1 and Figure 2 The organ chip 1 further includes a liquid inlet pipeline 30, which includes a liquid inlet pipe 31 and a liquid inlet filter 32. The liquid inlet pipe 31 connects the liquid inlet port 132 on the surface of the main body 10 and the liquid inlet filter 32. In this way, liquid can be introduced into the first cavity 11 through the liquid inlet pipe 31 connected to the liquid inlet filter 32, and the sealing performance is better.

[0091] In some embodiments, the liquid inlet pipe 31 and the liquid inlet filter 32, and the liquid inlet pipe 31 and the main body 10 can be connected via a Luer connector to improve the sealing performance between the liquid inlet pipe 31 and the liquid inlet filter 32, and between the liquid inlet pipe 31 and the main body 10, and meet high sealing requirements. Specifically, the liquid inlet pipe 31 and the liquid inlet filter 32 can be connected by interference fit at both ends of the Luer female connector 33; for example, the liquid inlet pipe 31 and the threaded end of the Luer female connector 33 are connected by interference fit, and the liquid inlet filter 32 and the pagoda end of the Luer female connector 33 are connected by interference fit. Specifically, the liquid inlet pipe 31 and the main body 10 can be connected by interference fit at both ends of the Luer male connector 34, which will not be described in detail.

[0092] In some embodiments, the liquid inlet filter 32 may be a Millex 0.22 μm filter, the Luer female connector 33 may be a 1.6 mm Luer female connector, and the Luer male connector 34 may be a 1.6 mm Luer male connector. The liquid inlet tube 31 may be a medical grade silicone tube.

[0093] In some embodiments, see Figure 1 and Figure 2 The organ chip 1 further includes a liquid outlet pipeline 40, which includes a liquid outlet pipe 41 and a liquid outlet filter 42, and the liquid outlet pipe 41 connects the liquid outlet port 142 on the surface of the main body 10 and the liquid outlet filter 42. In this way, the fluid in the first cavity 11 can be discharged through the liquid outlet pipe 41 connected to the liquid outlet filter 42, and the sealing performance is better.

[0094] In some embodiments, the liquid outlet pipe 41 and the liquid outlet filter 42, and the liquid outlet pipe 41 and the main body 10 can be connected via a Luer connector to improve the sealing performance between the liquid outlet pipe 41 and the liquid outlet filter 42, and between the liquid outlet pipe 41 and the main body 10, and meet high sealing requirements. Specifically, the liquid outlet pipe 41 and the liquid outlet filter 42 can be connected by interference fit at both ends of the Luer female connector 43; for example, the liquid outlet pipe 41 and the threaded end of the Luer female connector 43 are connected by interference fit, and the liquid outlet filter 42 and the pagoda end of the Luer female connector 43 are connected by interference fit. Specifically, the liquid outlet pipe 41 and the main body 10 can be connected by interference fit at both ends of the Luer male connector 44, which will not be described in detail.

[0095] In some embodiments, the liquid outlet filter 42 may be a Millex 0.22 μm filter, the Luer female connector 43 may be a 1.6 mm Luer female connector, and the Luer male connector 44 may be a 1.6 mm Luer male connector. The liquid outlet tube 41 may be a medical grade silicone tube.

[0096] In the description of the present application, it should be understood that the terms "first", "second", etc. are used for descriptive purposes only and should not be understood as indicating or implying relative importance. For those of ordinary skill in the art, the specific meanings of the above terms in the present application can be understood according to the specific circumstances. In addition, in the description of the present application, unless otherwise specified, "multiple" refers to at least two, for example, two, three, four, etc. "And / or" describes the association relationship of associated objects, indicating that three relationships may exist, for example, A and / or B can represent: A exists alone, A and B exist at the same time, and B exists alone. The character " / " generally indicates that the objects associated before and after are in an "or" relationship.

[0097] The above disclosure is only the preferred embodiment of the present application, which certainly cannot be used to limit the scope of rights of the present application. Therefore, equivalent changes made according to the claims of the present application are still within the scope covered by the present application.

Claims

1. An organ chip, characterized in that: include: A main body, formed with a first cavity, a second cavity located below the first cavity and connected to the first cavity, a liquid inlet communication port and a liquid outlet communication port connected to the first cavity and spaced from each other, the main body having a step surface located between the first cavity and the second cavity and facing the first cavity, the step surface including a first area and a second area connected to the first area; The microcolumn is located in the first cavity, the microcolumn is connected to the first area and protrudes from the first area, and the second area is a blank area.

2. The organ chip according to claim 1, characterized in that: The second cavity has two third side walls arranged opposite to each other along a first direction, wherein the first direction is perpendicular to the thickness direction of the main body; Each of the third side walls is correspondingly provided with at least one of the first regions, and each of the first regions is connected to one of the micro-columns.

3. The organ chip according to claim 2, characterized in that: Each of the third side walls is correspondingly provided with a plurality of the first areas, and the plurality of the first areas are arranged at intervals along the extension direction of the third side wall.

4. The organ chip according to claim 2, characterized in that: The main body is formed with a plurality of second cavities located below the first cavity and connected to the first cavity, the plurality of second cavities are arranged along the first direction, and each of the second cavities has two third side walls arranged opposite to each other along the first direction.

5. The organ chip according to claim 2, characterized in that: Along the first direction, the liquid inlet communication port and the liquid outlet communication port are located on two opposite sides of the first cavity.

6. The organ chip according to claim 1, characterized in that: The main body is formed with a liquid inlet cavity communicating with the first cavity, and the liquid inlet cavity is provided with the liquid inlet communication port; And / or, the main body is formed with a liquid outlet cavity connected with the first cavity, and the liquid outlet cavity is provided with the liquid outlet communication port.

7. The organ chip according to claim 1, characterized in that: The second zone connects the entire circumference of the first zone.

8. The organ chip according to any one of claims 1 to 7, characterized in that: The main body is formed with a plurality of the first cavities, the second cavities corresponding to each of the first cavities, the liquid inlet communication port and the liquid outlet communication port; The plurality of first cavities are arranged along a second direction, and the second direction is perpendicular to a thickness direction of the body.

9. The organ chip according to claim 8, characterized in that: The main body is further formed with a communication channel between two adjacent first cavities, and the communication channel connects the liquid outlet communication port corresponding to one of the two adjacent first cavities with the liquid inlet communication port corresponding to the other first cavity.

10. The organ chip according to claim 1, characterized in that: The subject includes: Base plate; a middle plate, the bottom plate being arranged below the middle plate and the second cavity being formed therebetween; and The cover plate is arranged above the middle plate and the first cavity is formed between the two.

11. The organ chip according to claim 10, characterized in that: An upper groove is provided on the upper surface of the middle plate, and the first cavity is formed between the inner wall of the upper groove and the lower surface of the cover plate; And / or, a lower groove is provided on the lower surface of the middle plate, and the second cavity is formed between the inner wall of the lower groove and the upper surface of the bottom plate.

12. The organ chip according to claim 1, characterized in that: The main body is also formed with a liquid inlet channel and a liquid outlet channel, the liquid inlet channel is connected to the liquid inlet communication port, and the liquid outlet channel is connected to the liquid outlet communication port; Wherein, the liquid inlet channel and the liquid outlet channel are located on the same side of the first cavity; and / or, at least a portion of the liquid inlet channel is bent; and / or, the organ chip further includes a bubble removal member connected to the liquid inlet channel.

13. The organ chip according to claim 1, characterized in that: The main body is also formed with a liquid inlet channel and a liquid outlet channel, the liquid inlet channel is connected to the liquid inlet communication port, and the liquid outlet channel is connected to the liquid outlet communication port; Wherein, the organ chip further includes a liquid inlet pipeline, the liquid inlet pipeline includes a liquid inlet pipe and a liquid inlet filter, the surface of the main body is formed with a liquid inlet port connected to the liquid inlet channel, the liquid inlet pipe connects the liquid inlet port and the liquid inlet filter; and / or, the organ chip further includes a liquid outlet pipeline, the liquid outlet pipeline includes a liquid outlet pipe and a liquid outlet filter, the surface of the main body is formed with a liquid outlet port connected to the liquid outlet channel, the liquid outlet pipe connects the liquid outlet port and the liquid outlet filter.

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