Three-channel film-free barrier chip

Abstract

The utility model relates to the technical field of biological chips, in particular to a three-channel membrane-free barrier chip, which comprises a plate body, a hydrogel channel and two culture fluid channels communicated with the hydrogel channel respectively are arranged in the plate body, barrier fences for preventing hydrogel in the hydrogel channel from flowing into the culture fluid channels are respectively arranged between the hydrogel channel and the two culture fluid channels; the device can be better used for simulating microenvironments such as an in-vivo blood vessel barrier, a blood brain barrier and an intestinal tract barrier, can be better used for studying interaction among multiple organ tissues and pharmacological and toxicological studies, and can be better used for vascularization studies; the device can be better used for researching the interaction between a perfusion vasculature and a target tissue and the anti-angiogenesis research, can be better used for researching the interaction between cells, can be better used for layering co-culture of different types of cells, and realizes the research of the cell interaction, the signal transduction between the cells, the migration and the like with related tissue structures.

Description

Technical Field:

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

[0002] An organ chip is a microfluidic cell culture device composed of polymers, etc. By simulating the human microphysiological environment in vitro, it can reconstruct the structure and function at the tissue level and organ level in vitro, and can reproduce the physiological and pathological characteristics of organs in vivo. As an alternative to traditional animal models and 2D monolayer models, organ chips have broad development prospects in the fields of life science research, disease simulation, new drug research and development, and precision medicine.

[0003] In the human body, nutrients and gases are transported to various parts of the body through blood vessels, and nutrient, gas, and metabolite exchanges are carried out through the organ-vessel interface; in order to simulate blood vessel functions, observe angiogenesis, vascularization, cell-cell interactions, cell migration, etc., and construct a more realistic drug screening and toxicology testing platform, in the existing research on organ chip technology, most still use porous membranes to construct the corresponding interface, that is, vascular endothelial cells and cells corresponding to organs are cultured on both sides of the porous membrane respectively to simulate the cell arrangement and interface function of the organ and the blood vessel interface. However, the method of adding a porous membrane puts relatively high requirements on the properties and biocompatibility of the porous membrane itself, and the presence of the porous membrane will also affect the free interaction and migration of cells between channels. On the other hand, the bonding method of the porous membrane in the chip is relatively complex. Summary of the Utility Model:

[0004] The purpose of the utility model is to provide a three-channel membrane-free barrier chip for the deficiencies existing in the prior art, which can be used to construct a growth environment closer to that of organisms, can ensure the authenticity and effectiveness of in vitro cell culture data research, can be better used to simulate microenvironments such as in vivo blood vessel barriers, blood-brain barriers, and intestinal barriers, can be better used to study the interactions between multiple organ tissues, as well as pharmacodynamic and toxicological studies, can be better used for vascularization research, can be better used to study the interaction between the perfused vasculature and the target tissue, as well as anti-angiogenesis research, can be better used for cell-cell interaction research, can be better used to co-culture different types of cells in layers, and realize the research of cell-cell interaction, cell-cell signal transduction, migration, etc. related to tissue structures, without using porous membranes and can avoid the problems existing in the construction using porous membranes.

[0005] To achieve the above object, the technical solution adopted by the present utility model is: a three-channel membrane-free barrier chip, including a plate body, wherein a hydrogel channel and two culture fluid channels respectively communicating with the hydrogel channel are provided in the plate body, and barrier fences for blocking the hydrogel in the hydrogel channel from flowing into the culture fluid channels are respectively provided between the hydrogel channel and the two culture fluid channels.

[0006] A further improvement to the above solution is that the barrier fence includes a plurality of barrier columns, and the barrier columns in the same barrier fence are arranged at equal intervals along the extending direction of the hydrogel channel.

[0007] A further improvement to the above solution is that the barrier column is a triangular column or an isosceles trapezoidal column, and isosceles trapezoidal column exchange ports are respectively formed between every two adjacent barrier columns in the same barrier fence.

[0008] A further improvement to the above solution is that the length of the barrier column is 0.2 - 0.25 mm, the width of the barrier column is 0.2 - 0.25 mm, the height of the barrier column is 0.8 - 1.2 mm, and the distance between every two adjacent barrier columns in the same barrier fence is 0.5 - 0.7 mm.

[0009] A further improvement to the above solution is that the plate body includes a bottom plate and a cover plate arranged on the bottom plate, the barrier column includes a bottom column arranged on the bottom plate and a top column arranged on the cover plate, and the top of the bottom column is in contact with the bottom of the top column.

[0010] A further improvement to the above solution is that the bottom column and the top column are in a symmetrical structure.

[0011] A further improvement to the above solution is that the plate body is further provided with a glue adding hole, two liquid adding holes, and two liquid discharging holes. The hydrogel channel includes a glue inlet section and a mass exchange glue section that are communicated with each other. The glue adding hole is communicated with the mass exchange glue section through the glue inlet section. The culture fluid channel includes a liquid inlet section, a mass exchange liquid section, and a liquid discharging section that are communicated with each other. The two liquid adding holes are respectively communicated with the corresponding mass exchange liquid sections through the corresponding liquid inlet sections, and the two liquid discharging holes are respectively communicated with the corresponding mass exchange liquid sections through the corresponding liquid discharging sections.

[0012] A further improvement to the above solution is that the mass exchange glue section and the two mass exchange liquid sections together form a mass exchange area. The glue adding port and the two liquid adding ports are arranged side by side along the X-axis direction and the glue adding port is located between the two liquid adding ports. The mass exchange area and the two liquid discharging ports are arranged side by side along the X-axis direction and the mass exchange area is located between the two liquid discharging ports. The glue adding hole, the two liquid adding holes, and the two liquid discharging holes and the mass exchange area are distributed in a 2X3 matrix.

[0013] A further improvement to the above solution is that the mass exchange gel segment and two mass exchange liquid segments together form a mass exchange area, and an observation window for observing the mass exchange area is provided on the plate body.

[0014] A further improvement to the above solution is that the glue inlet segment has a structure with an increasingly larger opening in the direction close to the mass exchange gel segment.

[0015] The beneficial effect of the present utility model lies in that: A three-channel membrane-free barrier chip provided by the present utility model includes a plate body, in which there is a hydrogel channel, and two culture fluid channels respectively communicating with the hydrogel channel. Barrier fences are respectively provided between the hydrogel channel and the two culture fluid channels to block the hydrogel in the hydrogel channel from flowing into the culture fluid channels.

[0016] The hydrogel channel of the present utility model and the two culture fluid channels are respectively demarcated by barrier fences. The hydrogel is restricted within the hydrogel channel by the two barrier fences and the hydrogel in the hydrogel channel is blocked from flowing into the two culture fluid channels. The hydrogel forms a gel interface at the junction of the barrier fence and the hydrogel channel to facilitate cell adhesion. The gel interface provides the substrate hardness required for cell growth, so that cells can be evenly attached and distributed on the gel interface. Different cells can be cultured in the two culture fluid channels, and the culture media in the two culture fluid channels can exchange substances through the hydrogel arranged in the hydrogel channel to meet the needs of the nutrients required for the growth of cells located in two different culture media. The gel interface can simulate the real interface in an organism, so that it can be used to construct a growth environment closer to that of an organism, ensure the authenticity and effectiveness of cell in vitro culture data research, and can be better used to simulate microenvironments such as in vivo vascular barriers, blood-brain barriers, and intestinal barriers, better used for studying the interactions between multiple organs and tissues, as well as pharmacodynamics and toxicology research, better used for vascularization research, better used for studying the interactions between perfused vasculature and target tissues and anti-angiogenesis research, better used for cell-cell interaction research, better used for co-culturing different types of cells in layers, and realizing the research of cell-cell interactions, cell-cell signal transduction, migration, etc. related to tissue structures, without the need to use porous membranes and can avoid the problems existing in the construction using porous membranes. Description of the drawings:

[0017] Figure 1 It is a structural schematic diagram of the present utility model.

[0018] Figure 2 It is an internal structural schematic diagram of the present utility model.

[0019] Figure 3 It is a cross-sectional structural schematic diagram of the barrier partition column of the present utility model.

[0020] Description of the reference numerals: plate body 1, bottom plate 11, cover plate 12, hydrogel channel 2, glue inlet section 21, mass exchange gel section 22, culture fluid channel 3, liquid inlet section 31, mass exchange liquid section 32, liquid outlet section 33, barrier fence 4, barrier partition column 41, bottom column 411, top column 412, isosceles trapezoidal column exchange port 42, glue adding hole 5, liquid adding hole 6, liquid outlet hole 7, mass exchange area 8, observation window 9. Detailed implementation manners:

[0021] The following further describes the present utility model with reference to the drawings. As Figures 1-3 shown, the present utility model includes a plate body 1. A hydrogel channel 2 and two culture fluid channels 3 respectively communicating with the hydrogel channel 2 are provided in the plate body 1. Barrier fences 4 for blocking the hydrogel in the hydrogel channel 2 from flowing into the culture fluid channels 3 are respectively provided between the hydrogel channel 2 and the two culture fluid channels 3. The two culture fluid channels 3 in this embodiment are symmetrically arranged on both sides of the hydrogel channel 2. Of course, in other embodiments, the two culture fluid channels 3 may be in other situations. The hydrogel channel 2 and the two culture fluid channels 3 of the present utility model are respectively demarcated by the barrier fences 4. The hydrogel is restricted in the hydrogel channel 2 by the two barrier fences 4 and the hydrogel in the hydrogel channel 2 is blocked from flowing into the two culture fluid channels 3. The hydrogel forms a gel interface at the junction of the barrier fence 4 and the hydrogel channel 2 to facilitate cell adhesion. The gel interface provides the substrate hardness required for cell growth, so that cells can be evenly attached and distributed on the gel interface. Different cells can be cultured in the two culture fluid channels 3, and the culture media in the two culture fluid channels 3 can perform mass exchange through the hydrogel provided in the hydrogel channel 2 to meet the nutritional requirements of cells located in two different culture media. The gel interface can simulate the real interface in an organism, so that it can be used to construct a growth environment closer to that of an organism, ensure the authenticity and effectiveness of cell in vitro culture data research, be better used to simulate microenvironments such as in vivo vascular barriers, blood-brain barriers, and intestinal barriers, be better used to study the interactions between multiple organs and tissues, as well as pharmacodynamics and toxicology research, be better used for vascularization research, be better used to study the interaction between the perfused vasculature and the target tissue, as well as anti-angiogenesis research, be better used for cell-cell interaction research, be better used for co-culturing different types of cells in layers, and realize the research of cell-cell interaction, cell-cell signal transduction, migration, etc. related to tissue structures, without using a porous membrane and being able to avoid the problems existing in the construction using a porous membrane.

[0022] The barrier fence 4 includes a plurality of barrier partition columns 41, which are arranged at equal intervals along the extending direction of the hydrogel channel 2 between the respective barrier partition columns 41 in the same barrier fence 4. In this embodiment, the hydrogel channel 2 is arranged in a straight line in the shape of a single line, so the extending direction of the hydrogel channel 2 in this embodiment is the length direction of the hydrogel channel 2.

[0023] The barrier partition column 41 is a triangular column or an isosceles trapezoidal column. An isosceles trapezoidal column exchange port 42 is respectively formed between every two adjacent barrier partition columns 41 in the same barrier fence 4, which can realize the mass exchange of the culture media in the two culture fluid channels 3 through the hydrogel in the hydrogel channel 2 while ensuring a good limiting effect on the hydrogel in the hydrogel channel 2.

[0024] The length of the barrier partition column 41 is preferably 0.2 - 0.25 mm. The length of the barrier partition column 41 in this embodiment is 0.23 mm. The width of the barrier partition column 41 is preferably 0.2 - 0.25 mm. The width of the barrier partition column 41 in this embodiment is 0.23 mm. The height of the barrier partition column 41 is preferably 0.8 - 1.2 mm. The height of the barrier partition column 41 in this embodiment is 1 mm. The distance between every two adjacent barrier partition columns 41 in the same barrier fence 4 is preferably 0.5 - 0.7 mm. The distance between every two adjacent barrier partition columns 41 in the same barrier fence 4 in this embodiment is 0.6 mm, which can better meet the hydrodynamics and thus can better limit the hydrogel in the hydrogel channel 2.

[0025] The plate body 1 includes a bottom plate 11 and a cover plate 12 arranged on the bottom plate 11. The barrier partition column 41 in this embodiment includes a bottom column 411 arranged on the bottom plate 11 and a top column 412 arranged on the cover plate 12. The top of the bottom column 411 is in contact with the bottom of the top column 412, and the bottom column 411 and the top column 412 are in a symmetrical structure; of course, in other embodiments, the bottom column 411 and the top column 412 of the barrier partition column 41 can also be in an asymmetrical structure, such as the bottom column 411 is longer and the top column 412 is shorter; of course, in other embodiments, the barrier partition column 41 can also be an integral structure and is not split into the bottom column 411 and the top column 412.

[0026] The plate body 1 is also provided with a glue adding hole 5, two liquid adding holes 6, and two liquid discharging holes 7. The hydrogel channel 2 includes a communicating glue inlet section 21 and a mass exchange glue section 22. The glue adding hole 5 is communicated with the mass exchange glue section 22 through the glue inlet section 21. The culture fluid channel 3 includes a communicating liquid inlet section 31, a mass exchange liquid section 32, and a liquid discharging section 33. The two liquid adding holes 6 are respectively communicated with the corresponding mass exchange liquid sections 32 through the corresponding liquid inlet sections 31. The two liquid discharging holes 7 are respectively communicated with the corresponding mass exchange liquid sections 32 through the corresponding liquid discharging sections 33. The adding method of the hydrogel and the culture fluid can be pump-free gravity-driven, or a microfluidic pump can be used to drive the flow of the hydrogel and the culture medium, so that the hydrogel and the culture medium can provide the fluid shear force environment required for cell growth.

[0027] The mass exchange glue section 22 and the two mass exchange liquid sections 32 together form a mass exchange area 8. The glue adding port, the two liquid adding ports are arranged side by side along the X-axis direction and the glue adding port is located between the two liquid adding ports. The mass exchange area 8, the two liquid discharging ports are arranged side by side along the X-axis direction and the mass exchange area 8 is located between the two liquid discharging ports. The glue adding hole 5, the two liquid adding holes 6, the two liquid discharging holes 7 and the mass exchange area 8 are distributed in a 2X3 matrix; the overall structure of the utility model is compact and reasonable, only occupying the positions of 6 holes of a standard 384-well plate, and can be better used for various researches and has better economic benefits.

[0028] The plate body 1 is provided with an observation window 9 for observing the mass exchange area 8. Through the observation window 9, the 3D culture can be monitored in real time, and the practicability is stronger.

[0029] The glue inlet section 21 is a structure with an opening gradually increasing along the direction close to the mass exchange glue section 22. Through the involute design, it is beneficial for the liquid glue, that is, the hydrogel, to flow stably and uniformly into the mass exchange glue section 22, avoiding disturbance and bubble formation.

[0030] Working principle:

[0031] Inject hydrogel into the hydrogel channel 2, culture different cells in the two culture fluid channels 3 respectively, limit the hydrogel within the hydrogel channel 2 through the two barrier fences 4 and prevent the hydrogel in the hydrogel channel 2 from flowing into the two culture fluid channels 3. The hydrogel forms a gel interface at the junction of the barrier fence 4 and the hydrogel channel 2 to facilitate cell adhesion. The gel interface provides the substrate hardness required for cell growth, so that cells can adhere and distribute evenly on the gel interface. The culture media in the two culture fluid channels 3 can conduct material exchange through the hydrogel arranged in the hydrogel channel 2 to meet the demand for nutrients required for the growth of cells located in the two different culture media. The gel interface can simulate the real interface in the organism, so that it can be used to construct a growth environment closer to the organism, can ensure the authenticity and effectiveness of cell in vitro culture data research, can be better used to simulate microenvironments such as in vivo vascular barrier, blood-brain barrier, intestinal barrier, etc., can be better used to study the interaction between multi-organ tissues, as well as pharmacodynamics and toxicology research, can be better used for vascularization research, can be better used to study the interaction between the perfused vasculature and the target tissue and anti-angiogenesis research, can be better used for cell-cell interaction research, can be better used for co-culturing different types of cells in layers, and realize the research on cell-cell interaction, cell-cell signal transduction, migration, etc. related to the tissue structure, without using a porous membrane and can avoid the problems existing in the construction by using a porous membrane.

[0032] Certainly, the above description is only the preferred embodiment of the present invention. Therefore, all equivalent changes or modifications made according to the structure, characteristics and principles described in the scope of the patent application of the present invention are included in the scope of the patent application of the present invention.

Claims

1. A three-channel membrane-free barrier chip, characterized in that: The invention comprises a plate body (1), wherein a hydrogel channel (2) and two culture fluid channels (3) respectively communicated with the hydrogel channel (2) are provided in the plate body (1); barrier fences (4) for blocking the hydrogel in the hydrogel channel (2) from flowing into the culture fluid channel (3) are respectively provided between the hydrogel channel (2) and the two culture fluid channels (3); the barrier fence (4) comprises a plurality of barrier columns (41), wherein the barrier columns (41) in the same barrier fence (4) are arranged at equal intervals along the extension direction of the hydrogel channel (2); the barrier columns (41) are triangular columns or isosceles trapezoidal columns, and isosceles trapezoidal column exchange ports (42) are respectively formed between two adjacent barrier columns (41) in the same barrier fence (4).

2. A three-channel membrane-free barrier chip according to claim 1, characterized in that: The length of the barrier column (41) is 0.2-0.25 mm, the width of the barrier column (41) is 0.2-0.25 mm, the height of the barrier column (41) is 0.8-1.2 mm, and the distance between each two adjacent barrier columns (41) in the same barrier fence (4) is 0.5-0.7 mm.

3. A three-channel membrane-free barrier chip according to claim 1, characterized in that: The plate body (1) comprises a bottom plate (11) and a cover plate (12) arranged on the bottom plate (11); the barrier column (41) comprises a bottom column (411) arranged on the bottom plate (11) and a top column (412) arranged on the cover plate (12); the top of the bottom column (411) is in contact with the bottom of the top column (412).

4. The three-channel membrane-free barrier chip according to claim 3, characterized in that: The bottom column (411) and the top column (412) are symmetrical structures.

5. The three-channel membrane-free barrier chip according to claim 1, characterized in that: The plate body (1) is further provided with a gel adding hole (5), two liquid adding holes (6), and two liquid outlet holes (7); the hydrogel channel (2) comprises a gel inlet section (21) and a substance exchange gel section (22) which are connected; the gel adding hole (5) is connected to the substance exchange gel section (22) via the gel inlet section (21); the culture fluid channel (3) comprises a liquid inlet section (31), a substance exchange liquid section (32), and a liquid outlet section (33) which are connected; the two liquid adding holes (6) are respectively connected to the corresponding substance exchange liquid section (32) via the corresponding liquid inlet section (31); and the two liquid outlet holes (7) are respectively connected to the corresponding substance exchange liquid section (32) via the corresponding liquid outlet section (33).

6. A three-channel membrane-free barrier chip according to claim 5, characterized in that: The substance exchange glue section (22) and the two substance exchange liquid sections (32) together form a substance exchange area (8); the glue adding port and the two liquid adding ports are arranged side by side along the X-axis direction and the glue adding port is located between the two liquid adding ports; the substance exchange area (8) and the two liquid outlets are arranged side by side along the X-axis direction and the substance exchange area (8) is located between the two liquid outlets; the glue adding hole (5), the two liquid adding holes (6), the two liquid outlet holes (7) and the substance exchange area (8) are arranged in a 2X3 matrix.

7. The three-channel membrane-free barrier chip according to claim 5, characterized in that: The substance exchange gel section (22) and the two substance exchange liquid sections (32) together form a substance exchange area (8), and an observation window (9) for observing the substance exchange area (8) is provided on the plate body (1).

8. The three-channel membrane-free barrier chip according to claim 5, characterized in that: The glue inlet section (21) is a structure whose opening gradually increases in a direction approaching the substance exchange glue section (22).

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