High-throughput living tissue chip box for in-vitro drug reaction detection

Abstract

The utility model provides a high-flux living tissue chip box for in-vitro drug reaction detection. The high-flux living tissue chip box is used for solving the problem of low flux of a PDEs culture device in the prior art. A high-flux living tissue chip box for in-vitro drug reaction detection comprises a base and a cover shell, a plurality of layers of supports are arranged between the base and the cover shell, each layer of support is provided with a plurality of culture cavities, each culture cavity is internally communicated with a plurality of liquid inlet branch pipes and a plurality of liquid outlet branch pipes, and the liquid inlet branch pipes are communicated with the liquid outlet branch pipes. A plurality of liquid inlets and a plurality of sample collection ports are formed in the housing, the liquid inlets are communicated with the liquid inlet branch pipes, and each sample collection port is communicated with one liquid outlet branch pipe; simultaneous treatment and analysis of a plurality of PDEs samples are realized, the flux is improved, and the requirements of large-scale drug screening and the like are met; each liquid inlet branch pipe is internally provided with a valve for controlling the opening and closing of the liquid inlet branch pipe, so that the flow of liquid in each culture cavity is accurately controlled, and different culture components are instantly mixed and used, so that the accurate simulation of complex culture conditions is realized.

Description

Technical Field

[0001] The utility model belongs to the technical field of biomedicine, and in particular relates to a high-throughput living tissue chip box for in vitro drug reaction detection. Background Art

[0002] The development of human tissue slice technology has provided a powerful tool for biomedical research, particularly in the fields of pathology, physiology, and drug screening. As an emerging in vitro model, tissue explants (PDEs), obtained through biopsy techniques, retain cell viability, intact tissue composition, and cellular distribution, providing a platform for research that more closely resembles the in vivo environment. These tissue slices not only preserve tissue architecture and microenvironmental components, such as stromal cells and tumor-infiltrating lymphocytes (TiLs), but also maintain the spatial characteristics of internal tissue components, which is particularly important for studying immune function and drug sensitivity testing.

[0003] However, while commercially available vibratome microtomes are capable of preparing fresh biopsies measuring 30-1000 μm, the uniformity of PDE thickness and the integrity of its tissue structure are crucial for reliable test results. Existing preparation methods are not specifically tailored to PDE drug susceptibility research and development, often failing to meet the demands of drug susceptibility testing. Furthermore, a lack of kits specifically for constructing and culturing PDEs for physiological and pathological studies and in vitro drug susceptibility testing, both domestically and internationally, limits the application of PDEs in these areas.

[0004] Recent advances in microfluidic gas-liquid culture technology offer new possibilities for the cultivation of PDEs, significantly improving their effectiveness and maintaining their activity and specific functions in ex vivo tissue sections. However, most culture devices can only support the cultivation of a single PDE, resulting in extremely low throughput and failing to meet the practical needs of applications such as large-scale drug screening. Utility Model Content

[0005] The utility model provides a high-throughput living tissue chip box for in vitro drug reaction detection, aiming to solve the problem of low throughput of PDEs culture devices in the prior art.

[0006] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0007] A high-throughput biopsy chip cartridge for in vitro drug reaction detection comprises a base and a cover, wherein several layers of supports are disposed between the base and the cover, wherein each layer of the supports is provided with several culture chambers, each culture chamber being connected to several liquid inlet branches and several liquid outlet branches, wherein the cover is provided with several liquid inlets and several sample collection ports, wherein the several liquid inlets are all connected to the liquid inlet branches, and each sample collection port is connected to a liquid outlet branch;

[0008] Each of the liquid inlet branch pipes is provided with a valve for controlling the on-off of the liquid inlet branch pipe.

[0009] In a preferred embodiment, a liquid outlet main pipe, a liquid inlet main pipe and several side branch passages are provided at the bottom of the cover shell, the several liquid outlet branch pipes are connected to the liquid outlet main pipe, the liquid inlet main pipe is connected to the liquid inlet, the inlet end of the side branch passage is connected to the liquid inlet main pipe, and the outlet end of the side branch passage is connected to the liquid inlet branch pipe.

[0010] Based on this scheme, the main outlet pipe connects all outlet branches, allowing liquid from each culture chamber to be discharged centrally for unified collection and processing. The main inlet pipe is responsible for transporting liquid to each culture chamber, ensuring a continuous and uniform liquid supply. The side branch pathways, with one end connected to the main inlet pipe and the other to the inlet branch pipes, guide liquid from the main pipe to the various branch pipes, ensuring smooth flow and precise distribution to each culture chamber.

[0011] In a preferred embodiment, the side branch passage is rotationally connected to the liquid inlet main pipe, and the rotation angle between the side branch passage and the liquid inlet main pipe is 30°-145°.

[0012] Based on this solution, by adjusting the angle between the side branch passages and the main inlet pipe, consistent inlet and outlet pressures can be achieved at all interfaces. This helps ensure even distribution of the drug solution within the piping system, avoiding uneven flow or dead zones caused by local pressure differences, thereby improving drug delivery efficiency and mixing. Furthermore, this angle adjustment can reduce eddy currents and turbulence in the drug solution flow, improving overall system efficiency.

[0013] In a preferred solution, the liquid inlet is located on the side wall of the cover shell, and the sample collection port is arranged on the top of the cover shell.

[0014] Based on the above solution, the liquid inlet on the side wall is convenient for connection to the external fluid delivery system, which can efficiently transport liquid into the system, while the sample collection port on the top is convenient for collecting and removing processed samples. This layout can reduce operational complexity and improve the work efficiency and safety of the entire system.

[0015] In a preferred solution, each culture chamber is connected to a liquid outlet branch and two liquid inlet branches, and two liquid inlets are provided on the side wall of the housing.

[0016] Based on this solution, each culture chamber is connected by one outlet and two inlet branches. This, combined with the dual inlet ports on the sidewall of the housing, improves fluid control precision and operational flexibility. Each culture chamber receives independent and precise liquid input. One inlet branch can be used to deliver the primary drug solution, while the other can be used to deliver other auxiliary liquids for mixing, enabling on-the-fly mixing to meet diverse needs.

[0017] In a preferred embodiment, the culture chamber comprises an upper chamber and a lower chamber, and a porous PET membrane is provided between the upper chamber and the lower chamber.

[0018] In a preferred embodiment, the upper chamber is connected to the liquid outlet branch, and the upper chamber is connected to the liquid inlet branch.

[0019] Based on this scheme, the porous PET membrane allows small molecules such as oxygen, nutrients, and metabolic waste to freely exchange between the upper and lower chambers, while preventing the passage of cells or larger molecules, mimicking the molecular exchange process of the extracellular matrix in the body. The upper chamber is connected to the inlet and outlet branches, allowing for precise control of fluid input and output.

[0020] In a preferred embodiment, the cross-sectional areas of the plurality of layers of supports gradually decrease from top to bottom.

[0021] In a preferred embodiment, three layers of supports are provided between the base and the cover, and each layer of supports is provided with eight culture cavities.

[0022] In a preferred solution, the valve includes a sealing rubber ring provided on the inner side wall of the liquid inlet branch pipe and a liquid inlet control plug matched with the sealing rubber ring.

[0023] Based on the above solution, the valve includes a sealing rubber ring arranged on the inner side wall of the liquid inlet branch and a liquid inlet control plug matched with the sealing rubber ring. This design allows for the instant mixing and use of different culture components. One liquid inlet pipe can pass the basic culture reagent, while the other liquid inlet pipe can pass the additive components that are easily ineffective. The liquid inlet control plug can completely block the opening of the liquid inlet pipe in the liquid inlet interface, thereby preventing the inflow of liquid and ensuring the stability and activity of the additive components. By flexibly matching the liquid inlet control plug, it is possible to achieve instant mixing of different culture components and individually control the addition of each component to ensure the accuracy and repeatability of the experiment.

[0024] The beneficial effects of the utility model are:

[0025] The utility model provides a high-throughput biopsy chip box for in vitro drug reaction detection. By arranging a multi-layer bracket between a base and a cover, each bracket layer is provided with multiple culture chambers, thereby realizing simultaneous processing and analysis of multiple PDEs samples, greatly improving throughput, and meeting the actual needs of applications such as large-scale drug screening; the valve arranged in each liquid inlet branch can control the on-off of the liquid, and the valve can accurately control the flow of liquid in each culture chamber, including the instant mixing of different culture components. For example, one liquid inlet pipeline can deliver basic culture reagents, and the other can deliver additive components that are easily ineffective, thereby realizing accurate simulation of complex culture conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following is a brief introduction to the drawings required for use in the embodiments. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without paying any creative work.

[0027] Figure 1 This is the first schematic diagram of the high-throughput living tissue chip box structure of the utility model.

[0028] Figure 2 This is the second schematic diagram of the high-throughput living tissue chip box structure of the present invention.

[0029] Figure 3 It is a structural schematic diagram of the culture chamber in the high-throughput living tissue chip box of the utility model.

[0030] Figure 4 It is a structural sectional view of the culture chamber in the utility model.

[0031] Figure 5 It is a schematic diagram of the bottom structure of the cover shell in the utility model.

[0032] Figure 6 It is a schematic diagram of the structure of the liquid inlet control plug in the utility model in the explosion state.

[0033] Notes on the attached numbers:

[0034] 1-cover; 2-sample collection port; 3-culture chamber; 4-liquid inlet branch pipe; 5-liquid inlet main pipe; 6-liquid outlet branch pipe; 7-liquid outlet main pipe; 8-side branch passage; 9-liquid inlet; 10-upper chamber; 11-PET porous membrane; 12-lower chamber; 13-base; 14-branch; 15-liquid inlet control plug; 151-sealing rubber plug; 152-rubber ring. DETAILED DESCRIPTION

[0035] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0036] See Figures 1-6 This embodiment provides a high-throughput biopsy chip cartridge for in vitro drug reaction detection, comprising a base 13 and a cover 1. Several layers of supports 14 are disposed between the base 13 and the cover 1. Each layer of the supports 14 is provided with several culture chambers 3. Each culture chamber 3 is connected to several liquid inlet branches 4 and several liquid outlet branches 6. The cover 1 is provided with several liquid inlets 9 and several sample collection ports 2. The several liquid inlets 9 are all connected to the liquid inlet branches 4, and each sample collection port 2 is connected to a liquid outlet branch 6.

[0037] Each of the liquid inlet branch pipes 4 is provided with a valve for controlling the on / off of the liquid inlet branch pipe 4 .

[0038] The bottom of the housing 1 is provided with a liquid outlet main pipe 7, a liquid inlet main pipe 5 and a plurality of side branch passages 8. The plurality of liquid outlet branches 6 are all connected to the liquid outlet main pipe 7. The liquid inlet main pipe 5 is connected to the liquid inlet port 9. The inlet end of the side branch passage 8 is connected to the liquid inlet main pipe 5, and the outlet end of the side branch passage 8 is connected to the liquid inlet branch pipe 4. The side branch passage 8 is rotatably connected to the liquid inlet main pipe 5, and the rotation angle between the side branch passage 8 and the liquid inlet main pipe 5 is 30°-145°.

[0039] Specifically, two liquid inlet main pipes 5 are provided at the bottom of the housing 1 , the inner diameters of the two liquid inlet pipes are 0.8-1.2 mm, the inner diameter of the main liquid outlet pipe is 0.8-1.2 mm, and the inner diameter of the pipe of the side branch passage 8 is 0.3-0.8 mm.

[0040] In addition, the liquid inlet 9 is located on the side wall of the housing 1 , and the sample collection port 2 is provided on the top of the housing 1 .

[0041] Specifically, the chip cover is provided with sample collection ports 2 connected to the liquid outlet branches 6 of the corresponding culture chambers 3. Each sample collection port 2 has an inner diameter of 0.5-1.0 mm and contains a circle of sealing strips with a thickness of 0.1-0.3 mm. After the chip box is assembled, the liquid inlet main pipe 5 in the culture chamber 3 is sealedly connected to the liquid inlet 9, and the liquid outlet main pipe 7 is sealedly connected to each sample collection port 2 on the cover, which can achieve sealing after connection, ensuring smooth inflow and outflow of liquid and no leakage.

[0042] The cross-sectional area of ​​the multiple layers of supports 14 gradually decreases from top to bottom. Three layers of supports 14 are provided between the base 13 and the housing 1, with each layer of supports 14 having eight culture chambers 3. Each culture chamber 3 is connected to a liquid outlet branch 6 and two liquid inlet branches 4. Two liquid inlets 9 are provided on the side wall of the housing 1.

[0043] Specifically, in the three-layer culture chamber 3, the inner diameter of the culture chamber 3 of the lower layer is 3-5 mm longer than that of the upper layer, so that a gap for accommodating the liquid outlet branch 6 and the liquid inlet branch 4 is provided between every two layers of the bracket 14. The eight culture chambers 3 of each layer are divided into two columns, each column is provided with four culture chambers 3, and the liquid inlet main pipe is arranged between the two columns of culture chambers 3.

[0044] The culture chamber 3 includes an upper chamber 10 and a lower chamber 12 , a porous PET membrane is provided between the upper chamber 10 and the lower chamber 12 , the upper chamber 10 is connected to the liquid outlet branch 6 , and the upper chamber 10 is connected to the liquid inlet branch 4 .

[0045] Specifically, the culture chamber 3 has an inner diameter of 12-24 mm, a wall thickness of 1.5-2.5 mm, and a height of 4-7 mm. It is divided into an upper chamber 10 and a lower chamber 12, which are separated by a porous PET membrane with a pore size of 0.1-8 mm. The lower layer has a height of 1.5-2 mm.

[0046] In addition, in order to control the on-off of the liquid in the liquid inlet branch pipe 4, based on any of the above solutions, the valve includes a sealing rubber ring arranged on the inner wall of the liquid inlet branch pipe 4 and a liquid inlet control plug 15 matched with the sealing rubber ring.

[0047] The following is a further explanation of the present invention in conjunction with its working principle:

[0048] A multi-layered support structure 14 is positioned between the base 13 and the housing 1. Multiple culture chambers 3 are distributed on each layer of support structure 14. Each culture chamber 3 is connected to the outside via an inlet branch 4 and an outlet branch 6 to facilitate the input and output of liquids. The housing 1 is equipped with multiple liquid inlets 9 and sample collection ports 2, connected to the inlet branch 4 and outlet branch 6, respectively, to facilitate the introduction of liquids and the collection of samples. Each inlet branch 4 is equipped with a valve that controls the flow of liquid, thereby precisely controlling the flow of liquid within each culture chamber 3, including the immediate mixing of different culture components. A liquid outlet main pipe 7, a liquid inlet main pipe 5 and a side branch passage 8 are provided at the bottom of the cover shell 1, wherein the liquid outlet branch pipe 6 is connected to the liquid outlet main pipe 7, the liquid inlet main pipe 5 is connected to the liquid inlet 9, and the side branch passage 8 connects the liquid inlet main pipe 5 to the liquid inlet branch pipe 4, and the side branch passage 8 and the liquid inlet main pipe 5 can be rotatably connected, and the rotation angle is 30°-145° to achieve flexible liquid distribution.

[0049] The present invention is not limited to the above optional implementation methods. Under the premise of not conflicting with each other, the various solutions can be combined arbitrarily. Anyone can derive other forms of products under the inspiration of the present invention. However, no matter what changes are made in their shape or structure, all technical solutions that fall within the scope defined by the claims of the present invention fall within the scope of protection of the present invention.

Claims

1. A high-throughput biopsy chip kit for in vitro drug response detection, characterized in that: The apparatus comprises a base and a cover, wherein a plurality of layers of supports are provided between the base and the cover, wherein each layer of the supports is provided with a plurality of culture chambers, wherein each culture chamber is connected to a plurality of liquid inlet branches and a plurality of liquid outlet branches, wherein the cover is provided with a plurality of liquid inlets and a plurality of sample collection ports, wherein the plurality of liquid inlets are connected to the liquid inlet branches, and each sample collection port is connected to a liquid outlet branch; Each of the liquid inlet branch pipes is provided with a valve for controlling the on-off of the liquid inlet branch pipe.

2. A high-throughput biopsy chip kit for in vitro drug response detection according to claim 1, characterized in that: A liquid outlet main pipe, a liquid inlet main pipe and several side branch passages are provided at the bottom of the cover shell. The several liquid outlet branches are all connected to the liquid outlet main pipe, the liquid inlet main pipe is connected to the liquid inlet, the inlet end of the side branch passage is connected to the liquid inlet main pipe, and the outlet end of the side branch passage is connected to the liquid inlet branch pipe.

3. A high-throughput biopsy chip kit for in vitro drug response detection according to claim 2, characterized in that: The side branch passage is rotationally connected to the liquid inlet main pipe, and the rotation angle between the side branch passage and the liquid inlet main pipe is 30°-145°.

4. The high-throughput biopsy chip kit for in vitro drug response detection according to claim 1, characterized in that: The liquid inlet is located on the side wall of the cover shell, and the sample collection port is arranged on the top of the cover shell.

5. The high-throughput biopsy chip kit for in vitro drug response detection according to claim 4, characterized in that: Each culture cavity is connected with a liquid outlet branch pipe and two liquid inlet branch pipes, and two liquid inlets are arranged on the side wall of the cover shell.

6. The high-throughput biopsy chip kit for in vitro drug response detection according to claim 1, characterized in that: The culture chamber comprises an upper chamber and a lower chamber, and a porous PET membrane is provided between the upper chamber and the lower chamber.

7. A high-throughput biopsy chip kit for in vitro drug response detection according to claim 6, characterized in that: The upper chamber is communicated with the liquid outlet branch pipe, and the upper chamber is communicated with the liquid inlet branch pipe.

8. The high-throughput biopsy chip kit for in vitro drug response detection according to claim 1, characterized in that: The cross-sectional areas of the multiple layers of supports gradually decrease from top to bottom.

9. The high-throughput biopsy chip kit for in vitro drug response detection according to claim 1, characterized in that: Three layers of supports are arranged between the base and the cover shell, and each layer of supports is provided with eight culture cavities.

10. The high-throughput biopsy chip kit for in vitro drug response detection according to claim 1, characterized in that: The valve comprises a sealing rubber ring arranged on the inner side wall of the liquid inlet branch pipe and a liquid inlet control plug matched with the sealing rubber ring.

Images