Membrane type two-channel barrier chip

Abstract

The utility model relates to the technical field of biochips, in particular to a membrane type two-channel barrier chip which comprises two fluid channels capable of being used for inoculating cells or organoids, each fluid channel comprises a liquid inlet section, a fluid exchange section and a liquid outlet section, the fluid exchange sections of the two fluid channels are overlapped in the vertical direction, and the liquid outlet sections of the two fluid channels are overlapped in the vertical direction. A porous membrane is arranged between the fluid exchange sections of the two fluid channels, and the fluid exchange sections of the two fluid channels realize material exchange and cell migration in the culture medium through the porous membrane; the device can be well used for constructing various single organ models with barrier functions, such as a blood brain barrier, a kidney barrier, an intestine barrier, a lung barrier and the like, can also realize multi-organ co-culture, and can well provide a good foundation for anti-tumor drug screening and tumor biological treatment method development.

Description

Technical field:

[0001] The utility model relates to the technical field of biochips, in particular to a membrane-type two-channel barrier chip. Background technology:

[0002] Organ-chips are microfluidic cell culture devices composed of polymers. By simulating the human microphysiological environment in vitro, they recreate the structure and function of tissues and organs at the in vitro level, reproducing the physiological and pathological characteristics of organs in vivo. As an alternative to traditional animal models and 2D monolayer models, organ-chips hold broad prospects in life science research, disease simulation, new drug development, and precision medicine.

[0003] Currently, there are generally three types of tumor research models, namely two-dimensional tumor cell culture, animal tumor models, and tumor organoids. Traditional 2D cell culture cannot reproduce the tumor microenvironment, and lacks cell-cell and cell-extracellular matrix interactions. Animal tumor models can make up for the shortcomings of cell models and simulate the in vivo environment of tumors, but they have the disadvantages of long culture cycles and high costs, and are unable to perform high-throughput drug screening and involve a series of problems such as experimental ethics. Tumor organoids maintain the 3D growth characteristics of tumors and can better reproduce the characteristics of parent tumors compared to 2D cell culture. They also have a short drug screening cycle, relatively simple operation, and are economical and practical. However, tumor organoids often come from single cell populations such as tumor tissues or cell lines, especially lack the tumor microenvironment composed of vascular endothelial cells and immune cells in solid tumors, and cannot provide the fluid shear force in the body.

[0004] In order to better study the interaction between tumor cells and peripheral blood vessels in the tumor microenvironment and provide a good foundation for anti-tumor drug screening and the development of tumor biotherapy, there is an urgent need for a chip that can be used to construct various single-organ models with barrier functions, such as the blood-brain barrier, kidney barrier, intestinal barrier, lung barrier, etc., and can also realize multi-organ co-culture. Utility model content:

[0005] The purpose of this utility model is to address the shortcomings of the existing technology and provide a membrane-type two-channel barrier chip, which can be well used to construct various single-organ models with barrier functions, such as the blood-brain barrier, kidney barrier, intestinal barrier, lung barrier, etc., and can also realize multi-organ co-culture, which can provide a good foundation for anti-tumor drug screening and the development of tumor biotherapy methods.

[0006] In order to achieve the above-mentioned purpose, the technical solution adopted by the present invention is: a membrane-type two-channel barrier chip, comprising two fluid channels that can be used to inoculate cells or organoids, the two fluid channels respectively including a liquid inlet section, a fluid exchange section, and a liquid outlet section, the fluid exchange sections of the two fluid channels are arranged to overlap in the up and down directions, and a porous membrane is provided between the fluid exchange sections of the two fluid channels, and the fluid exchange sections of the two fluid channels realize substance exchange and cell migration in the culture medium through the porous membrane.

[0007] A further improvement to the above solution is that the porous membrane includes a plurality of through holes, and the pore diameter of the through holes is 8-12 μm.

[0008] A further improvement to the above solution is that the porous membrane is horizontally arranged between the two fluid exchange sections.

[0009] A further improvement to the above solution is that the bending angle of the porous membrane is less than plus or minus 5 degrees.

[0010] A further improvement to the above solution is that the area of ​​the fluid exchange section is greater than or equal to 70 mm 2 .

[0011] A further improvement to the above solution is that the fluid exchange section is a cylindrical structure.

[0012] A further improvement to the above solution is that the diameter of the fluid exchange section is greater than or equal to 10 mm.

[0013] A further improvement to the above solution is that the height of the fluid exchange section is greater than or equal to 1 mm.

[0014] A further improvement to the above solution is that the thickness of the porous membrane is 8-12 μm.

[0015] A further improvement to the above solution is that the liquid inlet section and the liquid outlet section of the fluid channel are respectively located on both sides of the fluid exchange section, and the liquid inlet section and the liquid outlet section of the fluid channel are distributed in a straight line.

[0016] The beneficial effects of the utility model are as follows: the utility model provides a membrane-type two-channel barrier chip, comprising two fluid channels that can be used to inoculate cells or organoids, wherein the two fluid channels respectively include a liquid inlet section, a fluid exchange section, and a liquid outlet section, the fluid exchange sections of the two fluid channels being arranged to overlap in the vertical direction, and a porous membrane being provided between the fluid exchange sections of the two fluid channels, and the fluid exchange sections of the two fluid channels realizing substance exchange in the culture medium and cell migration through the porous membrane;

[0017] A microfluidic pump is used to provide continuous cell culture medium perfusion to the two fluid channels respectively, and cells or organoids are cultured in the two fluid channels respectively. The porous membrane can not only achieve the permeation and exchange of nutrients, inorganic salt ions and other substances in the two fluid channels, but also achieve transmembrane migration of cells of different sizes below 20 μm in the two fluid channels, thereby allowing cell-to-cell interaction and simulating the in vivo microenvironment. By arranging the porous membrane between the fluid exchange sections of the two fluid channels, the barrier membrane contact surface is more concentrated, and it is easier to construct multi-layer cell barriers, such as the blood-brain barrier, the kidney barrier, the intestinal barrier, the lung barrier, etc. The utility model can be well used to construct various single-organ models with barrier functions, such as the blood-brain barrier, the kidney barrier, the intestinal barrier, the lung barrier, etc., and can also achieve multi-organ co-culture, which can provide a good foundation for anti-tumor drug screening and the development of tumor biotherapy methods. Description of the drawings:

[0018] Figure 1 It is a structural diagram of the present utility model.

[0019] Figure 2 It is a schematic diagram of the internal structure of the utility model.

[0020] Description of reference numerals: fluid channel 1 , liquid inlet section 11 , fluid exchange section 12 , liquid outlet section 13 , porous membrane 2 , through hole 21 . Specific implementation method:

[0021] The present invention will be further described below with reference to the accompanying drawings. Figure 1-2As shown, the utility model includes two fluid channels 1 that can be used to inoculate cells or organoids, and the two fluid channels 1 respectively include a liquid inlet section 11, a fluid exchange section 12, and a liquid outlet section 13. The fluid exchange sections 12 of the two fluid channels 1 are arranged to overlap in the up and down directions, and a porous membrane 2 is provided between the fluid exchange sections 12 of the two fluid channels 1. The fluid exchange sections 12 of the two fluid channels 1 realize substance exchange and cell migration in the culture medium through the porous membrane 2; continuous cell culture medium perfusion is provided to the two fluid channels 1 respectively through a microfluidic pump, and cells or organoids are cultured in the two fluid channels 1 respectively. Through the porous membrane 2, not only nutrients, inorganic salt ions, etc. in the two fluid channels 1 can be realized The permeation and exchange of substances can also realize the transmembrane migration of cells of different sizes below 20 μm in the two fluid channels 1, thereby allowing cell-to-cell interaction and simulating the in vivo microenvironment; the utility model arranges the porous membrane 2 between the fluid exchange sections 12 of the two fluid channels 1, so that the contact surface of the barrier membrane is more concentrated, and it is easier to construct multi-layer cell barriers, such as the blood-brain barrier, the kidney barrier, the intestinal barrier, the lung barrier, etc.; the utility model can be well used to construct various single-organ models with barrier functions, such as the blood-brain barrier, the kidney barrier, the intestinal barrier, the lung barrier, etc., and can also realize multi-organ co-culture, which can provide a good foundation for the screening of anti-tumor drugs and the development of tumor biotherapy methods.

[0022] The porous membrane 2 includes multiple through holes 21. Nutrients, inorganic salt ions and other substances in the fluid exchange section 12 of the two fluid channels 1 are permeated and exchanged through the through holes 21 on the porous membrane 2. Cells in the fluid exchange section 12 of the two fluid channels 1 are migrated across the membrane through the through holes 21 on the porous membrane 2. The pore size of the through hole 21 is preferably 8-12 μm, and the thickness of the porous membrane 2 is preferably 8-12 μm.

[0023] The porous membrane 2 is horizontally arranged between the two fluid exchange sections 12. The bending angle of the porous membrane 2 is less than plus or minus 5 degrees. The porous membrane 2 remains straight, making it easier to construct multi-layer cell barriers, such as the blood-brain barrier, kidney barrier, intestinal barrier, lung barrier, etc.

[0024] The area of ​​the fluid exchange section 12 is greater than or equal to 70 mm 2 , the area is relatively large, allowing relatively larger cell clusters to grow, which can study cell-to-cell interactions for a long time. At the same time, it is convenient to observe cell morphology under the microscope and it is easier to construct multi-layer cell barriers, such as the blood-brain barrier, kidney barrier, intestinal barrier, lung barrier, etc.

[0025] The fluid exchange section 12 is a cylindrical structure with a diameter greater than or equal to 10 mm and a height greater than or equal to 1 mm, which can provide sufficient space for cell cluster growth and thus facilitate better observation and research.

[0026] The liquid inlet section 11 and the liquid outlet section 13 of the fluid channel 1 are respectively located on both sides of the fluid exchange section 12. The liquid inlet section 11 and the liquid outlet section 13 of the fluid channel 1 are arranged in a straight line. The cell culture medium flows sequentially through the liquid inlet section 11, the fluid exchange section 12, and the liquid outlet section 13 located in the same fluid channel 1.

[0027] Working principle:

[0028] A microfluidic pump is used to provide continuous perfusion of cell culture medium to the two fluid channels 1, and cells or organoids are cultured in the two fluid channels 1. The porous membrane 2 can not only achieve the permeation and exchange of nutrients, inorganic salt ions and other substances in the two fluid channels 1, but also achieve transmembrane migration of cells of different sizes below 20 μm in the two fluid channels 1, thereby allowing interaction between cells and simulating the in vivo microenvironment. By arranging the porous membrane 2 between the fluid exchange sections 12 of the two fluid channels 1, the barrier membrane contact surface is more concentrated, and it is easier to construct multi-layer cell barriers, such as the blood-brain barrier, the kidney barrier, the intestinal barrier, the lung barrier, etc. The utility model can be well used to construct various single-organ models with barrier functions, such as the blood-brain barrier, the kidney barrier, the intestinal barrier, the lung barrier, etc., and can also achieve multi-organ co-culture, which can provide a good foundation for the screening of anti-tumor drugs and the development of tumor biotherapy methods.

[0029] Of course, the above is only a preferred embodiment of the present invention, so all equivalent changes or modifications made according to the structure, features and principles described in the scope of the present invention patent application are included in the scope of the present invention patent application.

Claims

1. A membrane-type two-channel barrier chip, characterized by: The invention comprises two fluid channels (1) capable of being used for inoculating cells or organoids, wherein the two fluid channels (1) respectively comprise a liquid inlet section (11), a fluid exchange section (12), and a liquid outlet section (13); the fluid exchange sections (12) of the two fluid channels (1) are arranged to overlap in the vertical direction; a porous membrane (2) is provided between the fluid exchange sections (12) of the two fluid channels (1); and the fluid exchange sections (12) of the two fluid channels (1) achieve substance exchange in a culture medium and cell migration through the porous membrane (2).

2. The membrane-type two-channel barrier chip according to claim 1, characterized in that: The porous membrane (2) comprises a plurality of through holes (21), and the pore diameter of the through holes (21) is 8-12 μm.

3. The membrane-type two-channel barrier chip according to claim 1, characterized in that: The porous membrane (2) is arranged horizontally between two fluid exchange sections (12).

4. The membrane-type two-channel barrier chip according to claim 3, characterized in that: The bending angle of the porous membrane (2) is less than plus or minus 5 degrees.

5. The membrane-type two-channel barrier chip according to claim 1, characterized in that: The area of ​​the fluid exchange section (12) is greater than or equal to 70 mm 2 .

6. The membrane-type two-channel barrier chip according to claim 1, characterized in that: The fluid exchange section (12) is a cylindrical structure.

7. The membrane-type two-channel barrier chip according to claim 6, characterized in that: The diameter of the fluid exchange section (12) is greater than or equal to 10 mm.

8. A membrane-type two-channel barrier chip according to any one of claims 1 or 5-7, characterized in that: The height of the fluid exchange section (12) is greater than or equal to 1 mm.

9. The membrane-type two-channel barrier chip according to claim 1, characterized in that: The thickness of the porous membrane (2) is 8-12 μm.

10. The membrane-type two-channel barrier chip according to claim 1, characterized in that: The liquid inlet section (11) and the liquid outlet section (13) of the fluid channel (1) are respectively located on both sides of the fluid exchange section (12), and the liquid inlet section (11) and the liquid outlet section (13) of the fluid channel (1) are arranged in a straight line.

Images