CN219079546U - Cell and tissue culture organ chip - Google Patents

Cell and tissue culture organ chip Download PDF

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CN219079546U
CN219079546U CN202220702675.0U CN202220702675U CN219079546U CN 219079546 U CN219079546 U CN 219079546U CN 202220702675 U CN202220702675 U CN 202220702675U CN 219079546 U CN219079546 U CN 219079546U
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hydrogel
culture solution
channel
layer
chip
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请求不公布姓名
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Jiangsu Aiweide Biotechnology Co ltd
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Jiangsu Aiweide Biotechnology Co ltd
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Abstract

The utility model provides a cell and tissue culture organ chip. The chip comprises: the liquid storage chip structure layer is provided with at least one culture solution inlet and a hydrogel inlet; at least one culture solution inlet connecting hole and a hydrogel inlet connecting hole are arranged on the connecting layer; at least one culture solution channel and a hydrogel channel which are communicated are arranged on the fluid channel layer; the culture solution inlet connecting hole is respectively connected with the culture solution inlet and the culture solution channel, and the hydrogel inlet connecting hole is respectively connected with the hydrogel inlet and the hydrogel channel; the sealing layer is provided with a hydrophobic photosensitive material layer towards one side of the fluid channel layer, the hydrophilic and hydrophobic properties of the photosensitive material layer are changed by ultraviolet irradiation, a culture medium is guided to enter the culture solution channel, hydrogel enters the hydrogel channel, and the fluid flowing direction in the chip is guided to construct a layered structure.

Description

Cell and tissue culture organ chip
Technical Field
The utility model belongs to the technical fields of biological tissue engineering and biological medicine, and particularly relates to a cell and tissue culture organ chip.
Background
The human organ chip is based on a novel biochip technology, adopts micro-processing and micro-manufacturing means, and carries out accurate control on components such as cells/fluid/gas/extracellular microenvironment and the like in the chip through construction of a micro-channel, a micro-reaction chamber and other functional components, so as to generate human micro-tissues and micro-organs with biological functionality, provide living human biological samples for biological, chemical, medical and pharmaceutical research and the like, and provide practical experiment tests, wherein the organ chip is a research field integrating multiple subjects such as microfluidics, microelectronics, micromechanics, stem cells, biological materials and the like, and has the advantages of integration, low consumption, high flux, high simulation degree, quick analysis and the like. The organ chip technology has a revolutionary application prospect in the fields of new medicine research and development, personalized medicine and the like.
In order to better simulate the human tissue structure, a porous membrane is generally added into the chip to separate different types of cells, and the different types of cells are cultured on two sides of the membrane, so that the cell type and arrangement mode in the human body can be simulated. The mode of adding the porous membrane puts higher requirements on the property and biocompatibility of the membrane, different cells need to select the porous membrane with proper pore size, meanwhile, the porous membrane is required to have very good biocompatibility on various different cells, and on the other hand, the combination mode of the porous membrane in the chip is relatively complex.
Thus, the present utility model proposes a photowetted cell and tissue culture organ chip.
Disclosure of Invention
The utility model aims at solving at least one of the technical problems existing in the prior art and provides a cell and tissue culture organ chip.
The utility model provides a cell and tissue culture organ chip, comprising:
a liquid storage chip structure layer, a connecting layer, a fluid channel layer and a sealing layer which are sequentially laminated from top to bottom,
at least one culture solution inlet and a hydrogel inlet are arranged on the liquid storage chip structure layer;
at least one culture solution inlet connecting hole and a hydrogel inlet connecting hole are formed in the connecting layer;
at least one culture solution channel and a hydrogel channel which are communicated are arranged on the fluid channel layer; the culture solution inlet connecting hole is respectively connected with the culture solution inlet and the culture solution channel, and the hydrogel inlet connecting hole is respectively connected with the hydrogel inlet and the hydrogel channel;
the side of the sealing layer, which faces the fluid channel layer, is provided with a hydrophobic photosensitive material layer, and the hydrophilic and hydrophobic properties of the photosensitive material layer are changed by irradiating the photosensitive material layer with ultraviolet light so as to guide a culture medium to enter the culture solution channel, and hydrogel to enter the hydrogel channel.
Optionally, the number of the culture solution inlets is two, and the two culture solution inlets are respectively arranged at two sides of the hydrogel inlet;
the number of the culture solution inlet connecting holes is two, and the two culture solution inlet connecting holes are respectively arranged at two sides of the hydrogel inlet connecting hole;
the number of the culture solution channels is two, and the two culture solution channels are respectively arranged on two sides of the hydrogel channel.
Optionally, the photosensitive material layer is provided with a first hydrophobic area and a second hydrophobic area at intervals; wherein,,
the first hydrophobic region corresponds to a first connection region between one of the culture fluid channels and the hydrogel channel, and the second hydrophobic region corresponds to a second connection region between the other of the culture fluid channels and the hydrogel channel.
Optionally, the first hydrophobic region and the second hydrophobic region are elongated, and a length direction of the elongated shape is parallel to a length direction of the culture solution channel or the hydrogel channel.
Optionally, the first hydrophobic region and the second hydrophobic region are formed by the following method:
covering a layer of photosensitive material on the sealing layer to form a photosensitive material layer;
providing a preset mask, arranging the preset mask above the photosensitive material layer, and irradiating the preset mask by ultraviolet light to form the first hydrophobic region and the second hydrophobic region which are spaced apart on the photosensitive material layer.
Alternatively, the photosensitive material is an inorganic material or an organic material containing a photochromic functional group.
Alternatively, the photosensitive material is TiO 2 、ZnO、WO 3 、V 2 O 5 、SnO 2 Any one of azobenzene, spiropyran, bipyridine ethylene, stilbene and pyrimidine.
Optionally, the liquid storage chip structure layer is further provided with at least one culture solution outlet and a hydrogel outlet, and the connecting layer is further provided with at least one culture solution outlet connecting hole and a hydrogel outlet connecting hole; wherein,,
the culture solution outlet connecting hole is respectively connected with the culture solution outlet and the culture solution channel, and the hydrogel outlet connecting hole is respectively connected with the hydrogel outlet and the hydrogel channel.
Optionally, the number of the culture solution outlets is two, and the two culture solution outlets are respectively arranged at two sides of the hydrogel outlet;
the number of the culture solution outlet connecting holes is two, and the two culture solution outlet connecting holes are respectively arranged at two sides of the hydrogel outlet connecting hole.
Optionally, a membraneless three-layer layered structure is formed in the chip.
The utility model provides a cell and tissue culture organ chip, wherein the chip comprises: the liquid storage chip comprises a liquid storage chip structure layer, a connecting layer, a fluid channel layer and a sealing layer which are sequentially laminated from top to bottom, wherein at least one culture solution inlet and a hydrogel inlet are formed in the liquid storage chip structure layer; at least one culture solution inlet connecting hole and a hydrogel inlet connecting hole are arranged on the connecting layer; at least one culture solution channel and a hydrogel channel which are communicated are arranged on the fluid channel layer; the culture solution inlet connecting hole is respectively connected with the culture solution inlet and the culture solution channel, and the hydrogel inlet connecting hole is respectively connected with the hydrogel inlet and the hydrogel channel; the side of the sealing layer facing the fluid channel layer is provided with a hydrophobic photosensitive material layer, and the hydrophilic and hydrophobic properties of the sealing layer are changed by irradiating the photosensitive material layer with ultraviolet light so as to guide a culture medium to enter the culture solution channel, and hydrogel enters the hydrogel channel. The chip changes the hydrophilicity and hydrophobicity of the material through ultraviolet irradiation, so that the flow direction of fluid in the chip is guided to construct a layered structure, and the chip is simple in structure and convenient to operate.
Drawings
FIG. 1 is a schematic diagram of a cell and tissue culture organ chip according to one embodiment of the utility model;
FIG. 2 is a schematic diagram of a liquid storage chip structure layer according to an embodiment of the utility model;
FIG. 3 is a schematic structural diagram of a connection layer according to an embodiment of the present utility model;
FIG. 4 is a schematic view of a fluid channel layer according to an embodiment of the present utility model;
FIG. 5 is a schematic diagram showing a process of changing hydrophilicity and hydrophobicity of a photosensitive material coated with a blocking layer according to an embodiment of the present utility model.
Detailed Description
The present utility model will be described in further detail below with reference to the drawings and detailed description for the purpose of better understanding of the technical solution of the present utility model to those skilled in the art. It will be apparent that the described embodiments are some, but not all, embodiments of the utility model. All other embodiments, which can be made by a person skilled in the art without creative efforts, based on the described embodiments of the present utility model belong to the protection scope of the present utility model.
Unless specifically stated otherwise, technical or scientific terms used herein should be defined in the general sense as understood by one of ordinary skill in the art to which this utility model belongs. The use of "including" or "comprising" and the like in the present utility model is not intended to limit the shape, number, step, action, operation, component, original and/or group thereof referred to, nor exclude the presence or addition of one or more other different shapes, numbers, steps, actions, operations, components, original and/or group thereof. Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or order of the indicated features.
As shown in fig. 1 to 5, the present utility model provides a cell and tissue culture organ chip based on photo-wetting, comprising: the liquid storage chip structure layer A, the connecting layer B, the fluid channel layer C and the sealing layer E are sequentially laminated from top to bottom. The first liquid storage chip structure layer A is used for storing cell and organ tissue culture liquid, and is provided with at least one culture liquid inlet and a hydrogel inlet A3. The second connecting layer B is used for sealing the fluid channel in the third fluid channel layer C and connecting the liquid storage chip structure layer A with the fluid channel layer C, and at least one culture solution inlet connecting hole and a hydrogel inlet connecting hole B3 are formed in the second connecting layer B. The fluid channel layer C of the third layer is provided with at least one culture solution channel and a hydrogel channel C2 which are communicated with each other; the culture solution inlet connecting hole is respectively connected with the culture solution inlet and the culture solution channel, and the hydrogel inlet connecting hole B3 is respectively connected with the hydrogel inlet A3 and the hydrogel channel C2. The fourth layer is a sealing layer E for sealing the fluid channel layer, a hydrophobic photosensitive material layer D is arranged on one side of the sealing layer E, facing the fluid channel layer C, and the hydrophilic and hydrophobic properties of the photosensitive material layer are changed by irradiating the photosensitive material layer with ultraviolet light so as to guide a culture medium to enter a culture solution channel, and hydrogel enters a hydrogel channel.
The chip of the embodiment is provided with the photosensitive material layer with hydrophobicity on the sealing layer, and the flow direction of fluid in the fluid channel in the chip is guided based on the characteristic of light wetting, so that a membraneless layered structure is constructed.
In this embodiment, the material of the connection layer is not particularly limited, for example, a glass connection layer is used, and the connection layer has a porous glass layer structure due to the connection holes formed thereon. In addition, the material of the sealing layer is not particularly limited, and for example, a glass sealing layer, that is, a photosensitive material is coated on glass, is used.
Specifically, referring to fig. 2, the number of the culture solution inlets in the present embodiment is two, namely a first culture solution inlet A1 and a second culture solution inlet A5, wherein the first culture solution inlet A1 and the second culture solution inlet A5 are respectively disposed at two sides of the hydrogel inlet A3.
Referring to fig. 3, the number of the culture solution inlet connection holes is two, namely a first culture solution inlet connection hole B1 and a second culture solution inlet connection hole B5, wherein the first culture solution inlet connection hole B1 and the second culture solution inlet connection hole B5 are respectively disposed at two sides of the hydrogel inlet connection hole B3.
Referring to fig. 4, the number of the culture fluid channels is two, namely a first culture fluid channel C1 and a second culture fluid channel C3, wherein the first culture fluid channel C1 and the second culture fluid channel C3 are disposed on two sides of the hydrogel channel C2.
As shown in fig. 1 to 5, the first culture solution inlet connection hole B1 on the connection layer B is respectively communicated with the first culture solution inlet A1 and the first culture solution channel C1, and the second culture solution inlet connection hole B5 is respectively communicated with the second culture solution inlet A5 and the second culture solution channel C3, so that the culture medium passes through the first culture solution inlet A1 and the second culture solution inlet A5 of the chip and enters the fluid channel layer C through the first culture solution inlet connection hole B1 and the second culture solution inlet connection hole B5, and under the guidance of the hydrophilic and hydrophobic properties of the photosensitive material, enters the first culture solution channel C1 and the second culture solution channel C3, respectively, and the culture medium required for culture is provided for cells and organ tissues.
In addition, as shown in fig. 1 to 5, the hydrogel inlet connection hole B3 on the connection layer B is respectively connected with the hydrogel inlet A3 and the hydrogel channel C2, the hydrogel enters the fluid channel layer C from the hydrogel inlet A3 of the chip through the hydrogel inlet connection hole B3, the hydrogel enters the hydrogel channel C2 under the guidance of the hydrophilic and hydrophobic property of the photosensitive material, and after solidification, the chip is divided into a culture medium-hydrogel-culture medium membraneless three-layer structure.
Further, as shown in fig. 1 to 5, the photosensitive material layer D of the present embodiment is provided with a first hydrophobic region D1 and a second hydrophobic region D2 at intervals; wherein the first hydrophobic region D1 corresponds to a first connection region between the first culture fluid channel C1 and the hydrogel channel C2, and the second hydrophobic region D2 corresponds to a second connection region between the second culture fluid channel C3 and the hydrogel channel C2. That is, by disposing the water-repellent region correspondingly in the connection region of the culture liquid channel and the hydrogel channel, the fluid flow direction in the fluid pass-band layer can be restricted based on its hydrophobicity so that the culture liquid entering the fluid channel layer flows into the first culture liquid channel and the second culture liquid channel, respectively, without flowing into the hydrogel channel, and the hydrogel flows into the hydrogel channel, without flowing into the culture liquid channel, i.e., the hydrogel is located between the culture liquids, forming a membraneless three-layer structure.
It should be noted that, in this embodiment, specific shapes of the first hydrophobic region and the second hydrophobic region are not specifically limited, and the shapes of the first hydrophobic region and the second hydrophobic region may be the same or different.
As shown in fig. 1, the first hydrophobic region D1 and the second hydrophobic region D2 of the present embodiment are elongated, and the length direction of the elongated shape is parallel to the length direction of the culture fluid channel or the hydrogel channel, however, it is obvious to those skilled in the art that other shapes may be provided as long as the shapes are hydrophobic and the flow direction of the fluid can be restricted.
Specifically, the first hydrophobic region and the second hydrophobic region in this embodiment are formed by the following method: as shown in fig. 5, a sealing layer (glass substrate) is cleaned, and then a layer of photosensitive material is covered on the glass by sol-gel coating, spin coating, chemical vapor deposition, covalent modification and the like to form a photosensitive material layer F1 on the glass substrate, ultraviolet light is made to penetrate through a light transmission region of the mask F2 through designing and preparing the mask F2, and irradiates part of the surface of the photosensitive material coated glass substrate F3, so that a place with ultraviolet light irradiation is hydrophilic, a place without ultraviolet light irradiation is hydrophobic, a patterned structure F4 is generated, and a patterned hydrophilic-hydrophobic interphase region is obtained, namely a first hydrophobic region and a second hydrophobic region which are spaced apart are formed on the photosensitive material layer. Thus, when fluid flows over the surface of the photosensitive material, the flow of the fluid is limited by the hydrophobic structure of the photosensitive material, so that the fluid flows through the hydrophilic surface generated after the fluid is irradiated by ultraviolet light, and a culture medium-hydrogel-culture medium membraneless three-layer layered structure is built in the chip.
The photosensitive material of the present embodiment may be an inorganic material or an organic material containing a photochromic functional group, which is not particularly limited. For example, in some embodiments, the photosensitive material may employ TiO 2 、ZnO、WO 3 、V 2 O 5 、SnO 2 And the like. In other embodiments, the photosensitive material may also be an organic material such as azobenzene, spiropyran, bipyridine ethylene, stilbene, pyrimidine, etc.
The method for coating the photosensitive material layer on the sealing layer is integral coating, accurate channel construction is not needed, and the method is simple and convenient.
It should be understood that the hydrogel outlet and at least one culture fluid outlet are also disposed on the liquid storage chip structure layer of this embodiment. For example, as shown in connection with fig. 1 to 3, in some embodiments, the number of culture solution outlets is two, namely a first culture solution outlet A2 and a second culture solution outlet A6, respectively, and the two culture solution outlets are disposed on both sides of the hydrogel outlet A4, respectively.
Furthermore, the connection layer of the embodiment is further provided with a hydrogel outlet connection hole and at least one culture solution outlet connection hole. For example, as shown in connection with fig. 1 to 3, in some embodiments, the number of the culture solution outlet connection holes is two, namely, the first culture solution outlet connection hole B2 and the second culture solution outlet connection hole B6, and the two culture solution outlet connection holes are respectively arranged at both sides of the hydrogel outlet connection hole B4.
Further, as shown in fig. 1 to 5, the first culture solution outlet connection hole B2 is connected to the first culture solution outlet A2 and the first culture solution channel C1, respectively, and the second culture solution outlet connection hole B6 is connected to the second culture solution outlet A6 and the second culture solution channel C3, respectively, so that the redundant culture medium flows out from the first culture solution outlet A2 and the second culture solution outlet A6 of the chip through the first culture solution outlet connection hole B2 and the second culture solution outlet connection hole B6, respectively. Next, the hydrogel outlet connection hole B4 is connected to the hydrogel outlet A4 and the hydrogel channel C2, respectively, so that the excess hydrogel flows out of the hydrogel outlet A4 of the chip through the hydrogel outlet connection hole B4.
Based on the chip structure of the present embodiment, when the chip is used, the specific steps include:
first, hydrogel mixed with organ tissue is added from the hydrogel inlet A3 of the chip, and enters the hydrogel channel C2 through the hydrogel inlet connection hole B3.
Secondly, after the hydrogel is solidified, a hydrogel strip mixed with organ tissues is formed;
thirdly, adding culture medium of organ tissues from a culture solution inlet of the chip, and entering a culture solution channel through a culture solution inlet connecting hole to form a membraneless layered structure.
Specifically, the culture solution inlet of the present embodiment includes a first culture solution inlet A1 and a second culture solution inlet A5, the culture solution inlet connection hole includes a first culture solution inlet connection hole B1 and a second culture solution inlet connection hole B5, and the culture solution channel includes a first culture solution channel C1 and a second culture solution channel C3, so that the culture medium of the organ tissue is added from the first culture solution inlet A1 and the second culture solution inlet A5 of the chip, and enters into the first culture solution channel C1 and the second culture solution channel C3 through the first culture solution inlet connection hole B1 and the second culture solution inlet connection hole B5 to form a membraneless three-layer layered structure of the culture medium-hydrogel-culture medium.
It should be noted that the excess medium may flow out of the medium outlet of the chip, and the excess hydrogel may flow out of the hydrogel outlet of the chip.
It should be further noted that the driving mode of the liquid (e.g., the culture medium or the hydrogel) flow in this embodiment adopts any one of a pump-free gravity driving mode, an external peristaltic pump driving mode, and a syringe pump driving mode, so that the liquid can provide a fluid shear force environment required for organoid growth.
The cultivation of cell and tissue culture organ chips based on photowetting will be described in the following with specific examples:
example 1
This example is described for organoid culture, and is shown in connection with FIGS. 1-5:
1) Cleaning glass substrate, coating TiO on glass surface by sol-gel 2 A nanoparticle layer to form a photosensitive material layer on the glass encapsulation layer.
2) Chip parts are machined and the chips are assembled into a unitary body in the sequence of fig. 1.
3) Before the chip is used, the mask F2 is tightly adhered to the chip, and ultraviolet light is used for irradiating the chip to enable TiO to be formed on the surface of the glass sealing layer at the bottom layer of the chip 2 The nanoparticle layer produces a patterned structure F4 that renders the band-free sites hydrophobic, i.e., forms a first hydrophobic region and a second hydrophobic region, and the non-band sites hydrophilic.
4) Adding mixed organoid hydrogel from the hydrogel inlet A3 of the chip, and entering the hydrogel channel C2 through the hydrogel inlet connecting hole B3, wherein the TiO corresponding to the two sides of the hydrogel channel C2 2 The first hydrophobic region and the second hydrophobic region of the nanoparticle strip are hydrophobic such that the hydrogel solution follows the TiO 2 The hydrophilic surface of the nanoparticle flows without flowing into the first culture solution channel C1 and the second culture solution channel C3, and the excessive hydrogel flows out of the hydrogel outlet A4 of the chip through the hydrogel outlet connection hole B4.
5) After the hydrogel is cured, a hydrogel strip mixed with the organoid is formed.
6) Organoid medium is added from the first culture solution inlet A1 and the second culture solution inlet A5 of the chip, and enters the first culture solution channel C1 and the second culture solution channel C3 through the first culture solution inlet connecting hole B1 and the second culture solution inlet connecting hole B5. The redundant culture medium flows out from the first culture solution outlet A2 and the second culture solution outlet A6 of the chip through the first culture solution outlet connecting hole B2 and the second culture solution outlet connecting hole B6, and a membrane-free three-layer layered structure of the culture medium-hydrogel-culture medium is formed in the chip.
7) The liquid driving mode can be pump-free gravity driving, or an external peristaltic pump, a syringe pump and other devices can be used for driving the liquid to flow, so that the liquid can provide a fluid shear force environment required by organoid growth.
8) And (5) carrying out subsequent detection after the organoid culture is completed.
Example 2
This example is described with respect to the construction of an intestinal chip, and is shown in connection with fig. 1 to 5:
1) The glass substrate is cleaned, and a ZnO layer is coated on the surface of the glass through sol-gel to form a photosensitive material layer on the glass sealing layer.
2) Chip parts are machined and the chips are assembled into a unitary body in the sequence of fig. 1.
3) Before the chip is used, the mask F2 is tightly adhered to the chip, ultraviolet light is used for irradiating the chip, so that the ZnO layer on the surface of the glass sealing layer at the bottom layer of the chip generates a patterned structure F4, the area of the strip is hydrophobic, namely, a first hydrophobic area and a second hydrophobic area are formed, and the area without the strip is hydrophilic.
4) Hydrogel such as Matrigel/collagen/fibrin is added from a hydrogel inlet A3 of the chip, and enters a hydrogel channel C2 through a hydrogel inlet connecting hole B3, and because the first hydrophobic region and the second hydrophobic region of the ZnO layer strips corresponding to the two sides of the hydrogel channel C2 are hydrophobic, hydrogel solution flows along the hydrophilic surface of the ZnO layer and does not flow into the first culture solution channel C1 and the second culture solution channel C3 of the chip, and redundant hydrogel flows out of a hydrogel outlet A4 of the chip through a hydrogel outlet connecting hole B4.
5) After the hydrogel is cured, a hydrogel strip is formed.
6) Intestinal epithelial cells are added from the first culture solution inlet A1 of the chip, and enter and fill the first culture solution channel C1 through the first culture solution inlet connecting hole B1. Intestinal epithelial cells are adhered to the hydrogel surface at the boundary between the first culture solution channel C1 and the hydrogel channel C2. The intestinal epithelial cell culture medium is added from a first culture medium inlet A1 of the chip, enters and fills a first culture medium channel C1 through a first culture medium inlet connecting hole B1, and redundant culture medium flows out from a first culture medium outlet A2 of the chip through a first culture medium outlet connecting hole B2 to provide nutrition required by growth for intestinal cells.
7) Vascular endothelial cells are added from the second culture solution inlet A5 of the chip, and enter and fill the second culture solution channel C3 of the fluid channel through the second culture solution inlet connecting hole B5. The vascular endothelial cells are adhered to the hydrogel surface at the boundary between the hydrogel channel C2 and the second culture medium channel C3. Vascular endothelial cell culture medium is added from a second culture solution inlet A5 of the chip, enters and fills a second culture solution channel C3 through a second culture solution inlet connecting hole B5, and redundant culture medium flows out from a second culture solution outlet A6 of the chip through a second culture solution outlet connecting hole B6 to provide nutrition required by growth for endothelial cells.
8) The liquid driving mode can be pump-free gravity driving, or an external peristaltic pump, a syringe pump and other devices can be used for driving the liquid to flow, so that the liquid can provide a fluid shear force environment required by organoid growth.
9) After successful cell culture, an intestinal tract-endothelial organ model is constructed and completed for subsequent testing.
The utility model provides a cell and tissue culture organ chip, which has the following beneficial effects compared with the prior art: the chip disclosed by the utility model is irradiated by ultraviolet light to change the hydrophilicity and hydrophobicity of the photosensitive material, so that the flow direction of fluid in the chip is guided to construct a membraneless layered structure, the chip is simple in structure and convenient to operate, and the hardness of a substrate and the growth microenvironment required by the growth of various cells can be regulated through the composition of hydrogel.
It is to be understood that the above embodiments are merely illustrative of the application of the principles of the present utility model, but not in limitation thereof. Various modifications and improvements may be made by those skilled in the art without departing from the spirit and substance of the utility model, and are also considered to be within the scope of the utility model.

Claims (10)

1. A cell and tissue culture organ chip comprising:
a liquid storage chip structure layer, a connecting layer, a fluid channel layer and a sealing layer which are sequentially laminated from top to bottom,
at least one culture solution inlet and a hydrogel inlet are arranged on the liquid storage chip structure layer;
at least one culture solution inlet connecting hole and a hydrogel inlet connecting hole are formed in the connecting layer;
at least one culture solution channel and a hydrogel channel which are communicated are arranged on the fluid channel layer; the culture solution inlet connecting hole is respectively connected with the culture solution inlet and the culture solution channel, and the hydrogel inlet connecting hole is respectively connected with the hydrogel inlet and the hydrogel channel;
the side of the sealing layer, which faces the fluid channel layer, is provided with a hydrophobic photosensitive material layer, and the hydrophilic and hydrophobic properties of the photosensitive material layer are changed by irradiating the photosensitive material layer with ultraviolet light so as to guide a culture medium to enter the culture solution channel, and hydrogel to enter the hydrogel channel.
2. The chip of claim 1, wherein the number of the culture solution inlets is two, and the two culture solution inlets are respectively arranged at two sides of the hydrogel inlet;
the number of the culture solution inlet connecting holes is two, and the two culture solution inlet connecting holes are respectively arranged at two sides of the hydrogel inlet connecting hole;
the number of the culture solution channels is two, and the two culture solution channels are respectively arranged on two sides of the hydrogel channel.
3. The chip of claim 2, wherein the photosensitive material layer is provided with a first hydrophobic region and a second hydrophobic region at intervals; wherein,,
the first hydrophobic region corresponds to a first connection region between one of the culture fluid channels and the hydrogel channel, and the second hydrophobic region corresponds to a second connection region between the other of the culture fluid channels and the hydrogel channel.
4. The chip of claim 3, wherein the first hydrophobic region and the second hydrophobic region are elongated, and a length direction of the elongated shape is parallel to a length direction of the culture solution channel or the hydrogel channel.
5. The chip of claim 4, wherein the first hydrophobic region and the second hydrophobic region are formed by:
covering a layer of photosensitive material on the sealing layer to form a photosensitive material layer;
providing a preset mask, arranging the preset mask above the photosensitive material layer, and irradiating the preset mask by ultraviolet light to form the first hydrophobic region and the second hydrophobic region which are spaced apart on the photosensitive material layer.
6. The chip of claim 5, wherein the photosensitive material is an inorganic material or an organic material containing a photochromic functional group.
7. The chip of claim 6, wherein the photosensitive material is TiO 2 、ZnO、WO 3 、V 2 O 5 、SnO 2 Any one of azobenzene, spiropyran, bipyridine ethylene, stilbene and pyrimidine.
8. The chip of any one of claims 1 to 7, wherein the liquid storage chip structure layer is further provided with at least one culture solution outlet and a hydrogel outlet, and the connection layer is further provided with at least one culture solution outlet connection hole and a hydrogel outlet connection hole; wherein,,
the culture solution outlet connecting hole is respectively connected with the culture solution outlet and the culture solution channel, and the hydrogel outlet connecting hole is respectively connected with the hydrogel outlet and the hydrogel channel.
9. The chip of claim 8, wherein the number of the culture solution outlets is two, and the two culture solution outlets are respectively arranged at two sides of the hydrogel outlet;
the number of the culture solution outlet connecting holes is two, and the two culture solution outlet connecting holes are respectively arranged at two sides of the hydrogel outlet connecting hole.
10. The chip of any one of claims 1 to 7, wherein a membraneless three-layer layered structure is formed within the chip.
CN202220702675.0U 2022-03-29 2022-03-29 Cell and tissue culture organ chip Active CN219079546U (en)

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