CN115350736B - Detection device and detection method for skin inflammatory factors - Google Patents
Detection device and detection method for skin inflammatory factors Download PDFInfo
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- CN115350736B CN115350736B CN202211007815.3A CN202211007815A CN115350736B CN 115350736 B CN115350736 B CN 115350736B CN 202211007815 A CN202211007815 A CN 202211007815A CN 115350736 B CN115350736 B CN 115350736B
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Abstract
A device and a method for detecting skin inflammatory factors are provided, which are used for detecting skin inflammatory factors in vitro. The device for detecting the skin inflammatory factor comprises: a first microfluidic chip for constructing a skin inflammation model, and a second microfluidic chip for detecting skin inflammation factors; the first microfluidic chip is provided with at least one first liquid inlet, a plurality of culture cavities and at least one first liquid outlet, and the skin-like tissue arranged in each culture cavity is administrated through the first liquid inlet so as to construct a skin inflammation model; and the second microfluidic chip is provided with at least one second liquid inlet, at least one cavity and at least one second liquid outlet, and the liquid discharged from the first microfluidic chip enters the cavity through the second liquid inlet so as to detect skin inflammatory factors.
Description
Technical Field
The application relates to the field of microfluidic chips, in particular to a device and a method for detecting skin inflammatory factors.
Background
The human skin serves as a primary protective film for the human body, and functions to protect organs in the body from external environmental stimuli such as changes in temperature and humidity, ultraviolet rays, and harmful substances.
In the development of dermatological or cosmetic agents, it is often necessary to simulate the inflammatory conditions that may occur after administration of the agent or cosmetic agent to the skin and to conduct quantitative experiments.
However, there is currently no device and method that can quickly construct an inflammation model and perform quantitative detection.
Therefore, a new device and method for detecting skin inflammatory factor are needed to make up for the blank in the prior art.
Disclosure of Invention
The application aims to solve the technical problem of providing a novel detection device and a detection method for skin inflammatory factors, which are used for simply and rapidly constructing a skin inflammatory model and quantitatively detecting the skin inflammatory factors through a specially designed microfluidic chip and providing a rapid and effective platform for skin inflammatory test.
In order to solve the above problems, according to an aspect of the present application, there is provided a detection device for detecting skin inflammatory factor in vitro; the device for detecting the skin inflammatory factor comprises: a first microfluidic chip for constructing a skin inflammation model, and a second microfluidic chip for detecting skin inflammation factors; the first microfluidic chip is provided with at least one first liquid inlet, a plurality of culture cavities and at least one first liquid outlet, and the skin-like tissue arranged in each culture cavity is administrated through the first liquid inlet so as to construct a skin inflammation model; and the second microfluidic chip is provided with at least one second liquid inlet, at least one cavity and at least one second liquid outlet, and the liquid discharged from the first microfluidic chip enters the cavity through the second liquid inlet so as to detect skin inflammatory factors.
In some embodiments, the first microfluidic chip includes a first substrate and a first cover plate disposed opposite to each other, and a first flow channel layer disposed between the first substrate and the first cover plate, where the first flow channel layer is provided with a plurality of through holes, and each through hole and the first substrate form a culture cavity; each culture cavity is in fluid communication with one of the first fluid outlets; and, a flow channel is provided on a surface of the first flow channel layer facing the first substrate, the flow channel being in fluid communication with the plurality of culture chambers; the flow channel is configured to: so that the concentration of the liquid flowing through the flow channel is diluted in a gradient so that the concentration of the liquid flowing through the flow channel to the plurality of culture chambers forms a plurality of gradients.
In some embodiments, the flow channel comprises: a dilution flow channel, a connecting flow channel and a flow dividing flow channel; wherein the diluting flow channel comprises an N-stage branch flow channel, and an N-th-stage branch flow channel comprises n+1 sub flow channels; all sub-runners of the former-stage branch runner are in fluid communication with all sub-runners of the latter-stage branch runner through a connecting runner; each sub-runner of the first-stage branch runner is in fluid communication with a first liquid inlet; each sub-runner of the Nth-stage branch runner is connected with at least one split runner through a connecting runner and is further in fluid communication with at least one culture cavity; and N is a natural number greater than or equal to 3.
In some embodiments, each sub-runner of the branching runner of each stage has serpentine segments of uniform length.
In some embodiments, the connecting channel for connecting each sub-channel of the nth stage branch channel with at least one of the split channels is an annular channel.
In an embodiment of any one of the foregoing skin inflammatory factor detection apparatus, the first liquid inlet and the first liquid outlet are disposed in the first flow channel layer.
In some embodiments, a boss is disposed at a position of the first cover plate corresponding to each through hole of the first runner layer, where each boss is disposed on a surface of the first cover plate facing the first runner layer.
In some embodiments, each culture chamber is 9mm in diameter.
In an embodiment of any one of the foregoing skin inflammatory factor detection devices, the second microfluidic chip includes a second substrate and a second cover plate that are disposed opposite to each other, and a second flow channel layer disposed between the second substrate and the second cover plate, where the second liquid inlet and the second liquid outlet are disposed on the second cover plate; at least one groove is formed in the surface, facing the second cover plate, of the second flow channel layer, the groove and the second cover plate form the cavity of the second microfluidic chip, and a plurality of micropores are formed in the groove.
According to another aspect of the present application, there is also provided a method for detecting skin inflammatory factor. It will be appreciated by those skilled in the art that the method for detecting skin inflammatory factors is implemented using any of the above-described devices for detecting skin inflammatory factors.
In some embodiments, the detection method comprises the steps of: the step of constructing a skin inflammation model: constructing a skin inflammation model in a first microfluidic chip by using a plurality of gradient drug concentrations; and, a step of detecting a skin inflammatory factor: in a second microfluidic chip, magnetic microspheres are added in the liquid outlet of the first microfluidic chip entering the second microfluidic chip by applying electric field force to the second microfluidic chip so as to detect skin inflammatory factors; the first microfluidic chip is provided with at least one first liquid inlet, a plurality of culture cavities and at least one first liquid outlet, and the skin-like tissue arranged in each culture cavity is administrated through the first liquid inlet so as to construct the skin inflammation model; and the second microfluidic chip is provided with at least one second liquid inlet, at least one cavity and at least one second liquid outlet, and the liquid discharged from the first microfluidic chip enters the cavity through the second liquid inlet so as to detect skin inflammatory factors.
In some embodiments, the step of detecting a skin inflammatory factor comprises: a step of culturing the skin-like tissue: adding skin-like tissues into each culture cavity and inoculating a stratum corneum cell suspension, and adding a common culture medium into each culture cavity after the stratum corneum cells are stably attached for 4-8 hours so as to culture the skin-like tissues; a step of promoting differentiation of keratinocytes: exposing the common medium and the skin-like tissue in each culture cavity to air to promote the differentiation of the keratinocytes of the skin-like tissue; and, the step of administering: and adding medicines into each culture cavity through the first liquid inlet so as to stimulate the skin-like tissues and induce the skin inflammation factors to be generated, thereby constructing the skin inflammation model.
In some embodiments, the drug is Lipopolysaccharide (LPS).
In some embodiments, the magnetic microspheres comprise a fluorescent stain and are loaded with antibodies to skin inflammatory factors.
It will be appreciated by those skilled in the art that the magnetic microsphere may be any magnetic microsphere known or commercially available in the art that has magnetic properties and that includes a fluorescent dye.
In some preferred embodiments, the magnetic microsphere comprises two fluorescent dyes, and different brightness distributions can be obtained through different proportions of the two fluorescent dyes, so that specific detection of skin inflammatory factors can be realized.
In some embodiments, the skin inflammatory factor is at least one of TNF- α, IL-6, IL-10, or IL-1 α.
In some embodiments, the step of detecting a skin inflammatory factor comprises: collecting image information of the second microfluidic chip at different moments; and obtaining the concentration of the captured skin inflammatory factor according to the brightness change value of the magnetic microsphere at different moments in the obtained image information.
In some preferred embodiments, the step of detecting a skin inflammatory factor comprises: step 2.1: collecting image information of the second microfluidic chip at different moments; step 2.2: based on an edge detection algorithm, obtaining the edge of the bright spots in the image information acquired in the step 2.1, obtaining coordinates of the point positions of the edge by using a boundingRect function, and accumulating pixel values of all pixel points in a coordinate interval to obtain the brightness information of each bright spot in the image information acquired in the step 2.1; step 2.3: the brightness increase of 12% of the bright spots is defined as the magnetic microspheres capturing the skin inflammatory factors, and the number of the magnetic microspheres capturing the skin inflammatory factors is calculated by comparing the brightness increase values of the bright spots in the image information at different moments, so that the concentration of the skin inflammatory factors is obtained.
It will be appreciated by those skilled in the art that the skin-like tissue used in the present application may be commercially available skin-like tissue or may be constructed in a manner known in the art. As an example, the skin-like tissue may be a skin-like tissue constructed by 3D printing with a solution of hydrogel, collagen, and a suspension of human fibroblasts.
In the application, the in-vitro construction of the skin inflammation model with multi-gradient drug administration concentration is realized through the first micro-fluidic chip structure with specific design. Meanwhile, the application combines the structure of the first microfluidic chip and utilizes lipopolysaccharide drugs to induce and generate skin inflammation factors, successfully simulates the physiological microenvironment of human skin with a cutin dermis layer multilayer structure, replaces the cell experiment and animal experiment which are frequently used at present, provides a rapid and effective platform for skin inflammation test, and fills up the technical blank.
Drawings
FIG. 1 is a perspective view of a first microfluidic chip of a device for detecting skin inflammatory factors according to an embodiment of the present application;
fig. 2A is a schematic structural view of a surface a of the first runner layer 120 shown in fig. 1;
FIG. 2B is a perspective view of the first cover plate shown in FIG. 1;
fig. 3 is a schematic structural diagram of a second microfluidic chip of a device for detecting skin inflammatory factors according to an embodiment of the present application.
Detailed Description
The following describes in detail the specific embodiments of the device and method for detecting skin inflammatory factor provided by the present application with reference to the accompanying drawings.
The device for detecting skin inflammatory factor according to the present application will be described in detail with reference to fig. 1 to 3, wherein fig. 1 is a schematic structural diagram of a first microfluidic chip of the device for detecting skin inflammatory factor; fig. 2 is a schematic structural view of a surface a of the first microfluidic chip shown in fig. 1; fig. 3 is a schematic structural diagram of a second microfluidic chip of the skin inflammatory factor detection device.
The application relates to a detection device for skin inflammatory factors, which is used for detecting the skin inflammatory factors in vitro and comprises the following components: a first microfluidic chip 10 (shown in fig. 1 and 2) for constructing a skin inflammation model, and a second microfluidic chip 20 (shown in fig. 3) for detecting skin inflammatory factors.
The structure of the first microfluidic chip 10 is described in detail below with reference to fig. 1 and fig. 2A and 2B.
As shown in fig. 1, the first microfluidic chip 10 has at least one first liquid inlet 101, a plurality of culture chambers and at least one first liquid outlet 103, and is configured to apply drugs to skin-like tissue disposed in each culture chamber through the first liquid inlet 101, so as to construct a skin inflammation model. In this embodiment, as shown in fig. 1, the first microfluidic chip 10 has 2 first liquid inlets 101 and 12 first liquid outlets 102. Also, as shown in fig. 1, the first microfluidic chip 10 includes a first substrate 110 and a first cover plate 130 disposed opposite to each other, and a first flow channel layer 120 disposed between the first substrate 110 and the first cover plate 130. The first liquid inlet 101 and the first liquid outlet 102 are disposed on the first runner layer 120. And, the surface of the first runner layer 120 facing the first substrate 110 in fig. 1 is defined as a surface a.
Specifically, as shown in fig. 2A, the first flow channel layer 120 is provided with a plurality of through holes 121, and each through hole 121 may form the culture chamber with the first substrate 110 shown in fig. 1. Each culture chamber (and, in FIG. 2A, each through-hole 121 is in fluid communication with one of the first fluid outlets 103. The first flow channel layer 120 is configured to provide a flow channel on a surface A of the first substrate 110 shown in FIG. 1.
As shown in fig. 2A, the flow channel includes: a dilution flow path 122, a connecting flow path 123, and a flow diversion flow path 124. Wherein the dilution flow path 122 includes N-stage branch flow paths (122 a, 122N, and 122N), wherein the N-stage branch flow path 122N includes n+1 sub flow paths, N being a natural number of 3 or more. Also, as shown in FIG. 2A, each sub-flow passage 1221 of the first stage branch flow passage 122A is in fluid communication with a first liquid inlet 101; each sub-flow passage 1221 of the nth stage sub-flow passage 122N is connected to at least one of the sub-flow passages 124 through an annular connecting flow passage 1231, and is in fluid communication with at least one of the culture chambers (through-holes 121).
As shown in fig. 2A, all sub-runners 1221 of the former stage branch runner are in fluid communication with all sub-runners 1221 of the latter stage branch runner through a connecting runner 123; each of the sub-channels 1221 for connecting the nth fraction of the sub-channels 122N with the connecting channel 1231 of the at least one of the sub-channels 124 is an annular channel.
In this embodiment, as shown in fig. 2A, the diluting flow path 122 includes three branched flow paths 122N, wherein the first branched flow path includes 2 sub-flow paths 1221, the second branched flow path includes 3 sub-flow paths 1221, and the third branched flow path includes 4 sub-flow paths 1221. As shown in fig. 2A, each sub-runner 1221 of the branched runner 122N of each stage has a serpentine section of uniform length. It will be appreciated by those skilled in the art that the number of stages of the branching flow paths may be specifically set according to the gradient of the desired drug concentration. And, the diameter of each culture chamber (through-hole 121) was 9mm.
Thus, as shown in fig. 1 and 2A, in the first microfluidic chip 10, the concentration of the liquid flowing through the flow channel is diluted by the gradient by the above-described specific flow channel provided on the surface a of the first flow channel layer 120 facing the first substrate 110, so that the concentration of the liquid flowing through the flow channel to the plurality of culture chambers forms a plurality of gradients. For example, in the structure of the three-stage branch flow passage 122N shown in FIG. 2, the concentration of the drug entering the culture chamber (through-hole 121) is divided into four gradients.
As shown in fig. 2B, a boss 131 is disposed at a position of the first cover 130 corresponding to each through hole 121 of the first runner layer 120 shown in fig. 2A, and each boss 131 is disposed on a surface of the first cover 130 facing the first runner layer 120.
The structure of the second microfluidic chip 20 is described in detail below in conjunction with fig. 3.
As shown in fig. 3, the second microfluidic chip 20 has at least one second liquid inlet 201, at least one cavity and at least one second liquid outlet 202, and the liquid from the first microfluidic chip 10 shown in fig. 2A and 2B enters the cavity through the second liquid inlet 201 to detect skin inflammatory factors. As shown in fig. 3, the second microfluidic chip 20 includes a second substrate 210 and a second cover plate 230 disposed opposite to each other, and a second flow channel layer 220 disposed between the second substrate 210 and the second cover plate 230. The second liquid inlet 201 and the second liquid outlet 202 are disposed on the second cover 230; at least one groove 221 is disposed on a surface of the second flow channel layer 220 facing the second cover 230, the groove 221 and the second cover 230 form the cavity of the second microfluidic chip 20, and a plurality of micropores 222 are disposed in the groove 221.
Hereinafter, a method for detecting a skin inflammatory factor according to the present application using the above-described device for detecting a skin inflammatory factor will be described in detail with reference to fig. 1 to 3.
The detection method comprises the following steps:
step 1: construction of skin inflammation model
In the first microfluidic chip 10 shown in fig. 1 to 2B, a skin inflammation model is constructed with a plurality of gradients of drug concentration; the method comprises the steps of,
step 2: detection of skin inflammatory factors
In the second microfluidic chip 20 shown in fig. 3, skin inflammatory factors are detected by applying an electric field force to the second microfluidic chip 20 and adding magnetic microspheres in the liquid out of the first microfluidic chip 10 into the second microfluidic chip 20.
Specifically, the constructing a skin inflammation model in the step 1 includes:
step 1.1 culturing skin-like tissue: adding skin-like tissues into each culture cavity (namely, into the through holes 121 in fig. 2A) of the first microfluidic chip 10 shown in fig. 2A, inoculating a stratum corneum cell suspension, and adding a common culture medium into each culture cavity through the first liquid inlet 101 after the stratum corneum cells are stably attached for 4-8 hours so as to culture the skin-like tissues;
step 1.2 promotes keratinocyte differentiation: exposing the common medium and the skin-like tissue in each culture cavity to air to promote the differentiation of the keratinocytes of the skin-like tissue; as shown in fig. 1, since the first cover 130 covers the first flow channel layer 120, the first cover 130 may be removed to expose each culture chamber in this step, thereby promoting the differentiation and keratinization of the keratinocytes of the skin-like tissue; the method comprises the steps of,
step 1.3 dosing: adding a medicine into each culture cavity through the first liquid inlet 101 of the first microfluidic chip 10 shown in fig. 2A to stimulate and induce skin-like tissues to generate skin inflammatory factors, thereby constructing the skin inflammatory model; in this step, in order to form a plurality of gradients of drug concentration, drug is added through only one of the first liquid inlets 101. It will also be appreciated by those skilled in the art that when simulating the administration of a direct skin contact, the first cover plate 130 illustrated in FIG. 1 may also be removed to drip or smear directly over the culture chamber onto skin-like tissue.
In the above step, the drug is Lipopolysaccharide (LPS). The skin inflammatory factor is at least one of TNF-alpha, IL-6, IL-10 or IL-1 alpha.
After the skin inflammation model is built, the liquid out of the first microfluidic chip 10 is led out from the first liquid outlet 102 of the first microfluidic chip 10 shown in fig. 1, and the liquid out of the first microfluidic chip 10 is led into the second microfluidic chip 20 from the second liquid inlet 201 of the second microfluidic chip 20 shown in fig. 3 through, for example, pipeline connection. And, magnetic microspheres are added to the liquid discharged from the first microfluidic chip 10. For example, magnetic microspheres may be added through the second fluid inlet 201 as shown in fig. 3. The magnetic microsphere comprises a fluorescent dye and is loaded with an antibody of the skin inflammatory factor.
It will be appreciated by those skilled in the art that the magnetic microsphere may be any magnetic microsphere known or commercially available in the art that has magnetic properties and that includes a fluorescent dye. And preferably, the magnetic microsphere comprises two fluorescent dyes, and different brightness distribution can be obtained through different proportions of the two fluorescent dyes, so that the specific detection of skin inflammatory factors can be realized.
In the detection of skin inflammatory factor in the above step 2, in the second microfluidic chip 20 as shown in fig. 3, by applying an electric field force to the second microfluidic chip 20 and adding magnetic microspheres in the liquid out of the first microfluidic chip 10 into the second microfluidic chip 20, skin inflammatory factor is detected, and the method comprises the steps of: in some embodiments, the step of detecting a skin inflammatory factor comprises: collecting image information of the second microfluidic chip at different moments; and obtaining the concentration of the captured skin inflammatory factor according to the brightness change value of the magnetic microsphere at different moments in the obtained image information.
Specifically, the detecting skin inflammatory factor in the step 2 includes:
step 2.1: collecting image information of the second microfluidic chip at different moments;
step 2.2: based on an edge detection algorithm, obtaining the edge of the bright spots in the image information acquired in the step 2.1, obtaining coordinates of the point positions of the edge by using a boundingRect function, and accumulating pixel values of all pixel points in a coordinate interval to obtain the brightness information of each bright spot in the image information acquired in the step 2.1; the method comprises the steps of,
step 2.3: the brightness increase of 12% of the bright spots is defined as the magnetic microspheres capturing the skin inflammatory factors, and the number of the magnetic microspheres capturing the skin inflammatory factors is calculated by comparing the brightness increase values of the bright spots in the image information at different moments, so that the concentration of the skin inflammatory factors is obtained.
It will be appreciated by those skilled in the art that the skin-like tissue used in the present application may be commercially available skin-like tissue or may be constructed in a manner known in the art. As an example, the skin-like tissue may be a skin-like tissue constructed by 3D printing with a solution of hydrogel, collagen, and a suspension of human fibroblasts.
In the application, the in-vitro construction of the skin inflammation model with multi-gradient drug administration concentration is realized through the first micro-fluidic chip structure with specific design. Meanwhile, the application combines the structure of the first microfluidic chip and utilizes lipopolysaccharide drugs to induce and generate skin inflammation factors, successfully simulates the physiological microenvironment of human skin with a cutin dermis layer multilayer structure, replaces the cell experiment and animal experiment which are frequently used at present, provides a rapid and effective platform for skin inflammation test, and fills up the technical blank.
The foregoing is merely a preferred embodiment of the present application and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present application, which are intended to be comprehended within the scope of the present application.
Claims (14)
1. A device for detecting a skin inflammatory factor in vitro, the device comprising: a first microfluidic chip for constructing a skin inflammation model, and a second microfluidic chip for detecting skin inflammation factors; wherein,,
the first microfluidic chip is provided with at least one first liquid inlet, a plurality of culture cavities and at least one first liquid outlet, and the skin-like tissue arranged in each culture cavity is administrated through the first liquid inlet so as to construct a skin inflammation model; and, in addition, the processing unit,
the second microfluidic chip is provided with at least one second liquid inlet, at least one cavity and at least one second liquid outlet, and liquid discharged from the first microfluidic chip enters the cavity through the second liquid inlet so as to detect skin inflammatory factors;
the first microfluidic chip comprises a first substrate and a first cover plate which are oppositely arranged, and a first flow channel layer arranged between the first substrate and the first cover plate, wherein,
the first runner layer is provided with a plurality of through holes, and each through hole and the first substrate form a culture cavity;
each culture cavity is in fluid communication with one of the first fluid outlets; and, in addition, the processing unit,
a flow channel is arranged on the surface of the first flow channel layer facing the first substrate, and the flow channel is in fluid communication with the plurality of culture cavities; the flow channel is configured to: so that the concentration of the liquid flowing through the flow channel is diluted in a gradient so that the concentration of the liquid flowing to the plurality of culture chambers through the flow channel forms a plurality of gradients;
the second microfluidic chip comprises a second substrate and a second cover plate which are oppositely arranged, and a second flow channel layer arranged between the second substrate and the second cover plate, wherein,
the second liquid inlet and the second liquid outlet are arranged on the second cover plate;
at least one groove is formed in the surface, facing the second cover plate, of the second flow channel layer, the groove and the second cover plate form the cavity of the second microfluidic chip, and a plurality of micropores are formed in the groove.
2. The device for detecting skin inflammatory factor as defined in claim 1, wherein the flow channel comprises: a dilution flow channel, a connecting flow channel and a flow dividing flow channel; wherein,,
the dilution flow channel comprises an N-stage branch flow channel, wherein an nth-stage branch flow channel comprises n+1 sub flow channels;
all sub-runners of the former-stage branch runner are in fluid communication with all sub-runners of the latter-stage branch runner through a connecting runner;
each sub-runner of the first-stage branch runner is in fluid communication with a first liquid inlet;
each sub-runner of the Nth-stage branch runner is connected with at least one split runner through a connecting runner and is further in fluid communication with at least one culture cavity; and, in addition, the processing unit,
n is a natural number greater than or equal to 3.
3. The device for detecting skin inflammatory factor as claimed in claim 2, wherein each sub-flow path of the branched flow path of each stage has a serpentine section of uniform length.
4. The apparatus for detecting skin inflammatory factor according to claim 2, wherein the connecting flow path for connecting each sub-flow path of the nth stage branch flow path with at least one of the split flow paths is an annular flow path.
5. The device for detecting skin inflammatory factor according to any one of claims 1 to 4, wherein the first liquid inlet and the first liquid outlet are provided in the first flow channel layer.
6. The device for detecting skin inflammatory factor according to claim 5, wherein a boss is disposed at a position of the first cover plate corresponding to each through hole of the first runner layer, and each boss is disposed on a surface of the first cover plate facing the first runner layer.
7. The device for detecting skin inflammatory factor according to claim 5, wherein each culture chamber has a diameter of 9mm.
8. A method for detecting skin inflammatory factors, the method comprising the steps of:
the step of constructing a skin inflammation model: constructing a skin inflammation model in a first microfluidic chip by using a plurality of gradient drug concentrations; the method comprises the steps of,
detecting skin inflammatory factors: in a second microfluidic chip, magnetic microspheres are added in the liquid outlet of the first microfluidic chip entering the second microfluidic chip by applying electric field force to the second microfluidic chip so as to detect skin inflammatory factors; wherein,,
the first microfluidic chip is provided with at least one first liquid inlet, a plurality of culture cavities and at least one first liquid outlet, and the skin-like tissue arranged in each culture cavity is administrated through the first liquid inlet so as to construct the skin inflammation model; and, in addition, the processing unit,
the second microfluidic chip is provided with at least one second liquid inlet, at least one cavity and at least one second liquid outlet, and liquid discharged from the first microfluidic chip enters the cavity through the second liquid inlet so as to detect skin inflammatory factors.
9. The method of detecting according to claim 8, wherein the step of detecting the skin inflammatory factor comprises:
a step of culturing the skin-like tissue: adding skin-like tissues into each culture cavity and inoculating a stratum corneum cell suspension, and adding a common culture medium into each culture cavity after the stratum corneum cells are stably attached for 4-8 hours so as to culture the skin-like tissues;
a step of promoting differentiation of keratinocytes: exposing the common medium and the skin-like tissue in each culture cavity to air to promote the differentiation of the keratinocytes of the skin-like tissue; the method comprises the steps of,
the administration step: and adding medicines into each culture cavity through the first liquid inlet so as to stimulate the skin-like tissues and induce the skin inflammation factors to be generated, thereby constructing the skin inflammation model.
10. The method of claim 8, wherein the drug is lipopolysaccharide.
11. The method of claim 8, wherein the magnetic microsphere comprises a fluorescent dye and is loaded with antibodies to skin inflammatory factors.
12. The method of claim 9 or 10, wherein the skin inflammatory factor is at least one of TNF- α, IL-6, IL-10, or IL-1 α.
13. The method of detecting according to claim 12, wherein the step of detecting the skin inflammatory factor comprises:
collecting image information of the second microfluidic chip at different moments;
and obtaining the concentration of the skin inflammatory factor according to the brightness change values of the magnetic microspheres at different moments in the obtained image information.
14. The method of detecting according to claim 12, wherein the step of detecting the skin inflammatory factor comprises:
a) Collecting image information of the second microfluidic chip at different moments;
b) Based on an edge detection algorithm, obtaining the edge of the bright spots in the image information acquired in the step a), obtaining the coordinates of the point positions of the edge by using a boundingRect function, and accumulating the pixel values of all the pixel points in the coordinate interval to obtain the brightness information of each bright spot in the image information acquired in the step a); the method comprises the steps of,
and c), defining that the brightness of the bright spots is increased by 12%, namely the magnetic microspheres capturing the skin inflammatory factors, and calculating the number of the magnetic microspheres capturing the skin inflammatory factors by comparing the brightness increase values of the bright spots in the image information at different moments, so as to obtain the concentration of the skin inflammatory factors.
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