CN111349564A - Bionic skin chip for drug test - Google Patents
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Abstract
The invention discloses a bionic skin chip for drug test, which relates to the technical field of organ chips and comprises an upper layer chip, a middle layer chip, a porous membrane and a lower layer chip which are sequentially arranged from top to bottom; the bottom surface of the upper layer chip is provided with a sunken gas channel, and the middle layer chip is provided with a through groove corresponding to the gas channel; the upper surface of the lower chip is provided with at least three sunken Tesla micro-mixers, a first inlet channel, a first main channel, a collecting channel and a first outlet channel; the upper surface of the porous membrane covers below the through grooves, and the lower surface of the porous membrane covers on the collecting channel. The invention has the beneficial effects that: the drug test bionic skin chip provided by the invention can provide a gas-liquid phase culture environment for skin culture, realize bionic gas-liquid phase skin tissue culture and better simulate a human body microenvironment.
Description
Technical Field
The invention relates to the technical field of organ chips, in particular to a drug test bionic skin chip.
Background
The skin is the largest organ of the human body and serves as a physiological barrier to wrap the muscles and bones to protect tissues and organs in the body. However, skin is often exposed to a wide range of biochemical agents (e.g., cosmetics, skin detergents, etc.), ultraviolet light, pathogens, environmental pollutants, and microorganisms. The rapid increase in these factors can cause various skin reactions such as skin inflammation, irritation, allergy and even skin cancer. However, animal skin differs greatly from human skin in terms of thickness, hair density, and appendages, and therefore animal model-based studies are limited. Furthermore, with european legislation prohibiting the testing of cosmetic ingredients with animals, the number of industrial chemicals that must be risk assessed increases. Therefore, there is a strong need in the cosmetic, pharmacological, and toxicological arts for reliable, reproducible, high-throughput alternatives to animal testing.
For human skin substitutes, three-dimensional human skin models derived from human cell lines are the most advanced in vitro substitution methods. Compared with monolayer cell culture, the three-dimensional human skin model can better simulate the cell tissues and functions, lipid composition and differentiation, metabolic capacity of natural skin and retain the polarization of cells.
In recent years, the micro-fluidic technology and the micro-processing technology are rapidly developed, so that possibility is provided for in vitro simulation similar to human body microenvironment, a three-dimensional tissue culture environment can be provided, nutrients are supplied to tissues, wastes are timely removed, and a proper shear rate is provided, so that in vitro simulation of human organs is realized. For example, patent CN110408538A discloses a liver chip with a multi-lobular integrated structure, which is capable of highly simulating the liver microstructure in structure and function.
However, the skin chips in the prior art are few, and the skin chips in the prior art cannot analyze the influence of the drugs with different concentrations on skin tissues.
Disclosure of Invention
The invention aims to provide a drug test bionic skin chip capable of analyzing the influence of drugs with different concentrations on skin tissues.
The invention solves the technical problems through the following technical means:
a bionic skin chip for drug test comprises an upper chip, a middle chip, a porous membrane and a lower chip which are arranged in sequence from top to bottom;
the bottom surface of the upper layer chip is provided with a sunken gas channel, and the middle layer chip is provided with a through groove corresponding to the gas channel;
the upper surface of the lower chip is provided with at least three sunken Tesla micro-mixers, a first inlet channel, a first main channel, a collecting channel and a first outlet channel, the Tesla micro-mixers are arranged in parallel, channel inlets of the Tesla micro-mixers are connected with the first main channel, the first inlet channels are positioned in the middle of the adjacent Tesla micro-mixers, one end of each first inlet channel is communicated with the first main channel, channel outlets of the Tesla micro-mixers are communicated with the collecting channel, and the first outlet channels are communicated with the collecting channel;
the upper surface of the porous membrane covers below the through grooves, and the lower surface of the porous membrane covers on the collecting channel.
The working principle is as follows: covering the porous membrane on the collecting channel, then putting the middle chip, putting the prepared skin tissue into the through groove, and finally putting the upper chip. When in operation, the medicines with different concentrations enter the first main channel from different first inlet channels, because the depressed Tesla micro-mixers are arranged in parallel, and the first inlet channels are all positioned at the middle parts of the adjacent Tesla micro-mixers, the medicines in the adjacent first inlet channels can enter the depressed channels of the Tesla micro-mixers between the adjacent first inlet channels simultaneously after being mixed, when the number of the Tesla micro-mixers is two, the Tesla micro-mixers only contain the medicines with one concentration, when the number of the Tesla micro-mixers is at least three, the medicines with different concentrations in the Tesla micro-mixers on the non-two sides simultaneously flow in and are quickly and efficiently mixed by the Tesla micro-mixers to form the medicines with stable concentration gradient, then the medicines enter the collecting channel through the channel outlets of the plurality of Tesla micro-mixers, because the lower surface of the porous membrane covers on the collecting channel, the medicine passes through the porous membrane to be supplied to skin tissue, and simultaneously sterile air is introduced from the air channel, because the sunken air channel corresponds to the through groove, the sterile air introduced in the air channel generates air flow to the skin tissue in the through groove, a gas-liquid phase culture environment is provided for the skin tissue, and skin tissue metabolites penetrate through the porous membrane to enter the medicine, and flow into the first outlet channel from the collecting channel after substance exchange.
Has the advantages that: the drug test bionic skin chip provided by the invention can provide a gas-liquid phase culture environment for skin culture, realize bionic gas-liquid phase skin tissue culture and better simulate a human body microenvironment;
the bionic skin chip for testing the medicine has a simple structure, and can quickly and efficiently mix the medicine by adopting the Tesla micro-mixer, so that a stable medicine concentration gradient is formed, and the efficiency and the reliability of the medicine test are improved.
The skin chip in the prior art can not be applied to drug screening or drug testing, but compared with the skin chip in the prior art, the drug testing bionic skin chip can be used for gas-liquid phase culture and can also be used for drug toxicity testing or drug screening simultaneously, so that the detection efficiency is further improved.
The skin tissue metabolites in the first outlet channel can be collected and monitored in real time, so that the influence of different gradient concentrations of the drug on the skin tissue can be monitored.
The gas channel can simulate the human skin microenvironment, and the gas-liquid phase culture is favorable for the skin tissue produced in vitro to form the cuticle.
Preferably, the tesla micro-mixers include multiple stages of tesla micro-mixers, the multiple stages of tesla micro-mixers are sequentially connected in series, an outlet channel of any one tesla micro-mixer in a previous stage is positioned in the middle of an inlet channel of an adjacent tesla micro-mixer in a next stage, and the number of the tesla micro-mixers in the next stage is one more than that of the tesla micro-mixers in the previous stage.
Preferably, the multistage tesla micromixer comprises a first stage tesla micromixer and a second stage tesla micromixer; the channel inlets of the first stage Tesla micro-mixers are connected with a first main channel, and the first inlet channels are positioned in the middle of the adjacent first stage Tesla micro-mixers;
the channel inlet of the second stage Tesla micro-mixer is provided with a second main channel, the channel inlet of the second stage Tesla micro-mixer is communicated with the second main channel, the channel outlet of the first stage Tesla micro-mixer is positioned in the middle of the adjacent second stage Tesla micro-mixer, and the channel outlet of the second stage Tesla micro-mixer is communicated with the collecting channel.
Preferably, the number of the first stage tesla micro-mixers is three, the number of the second stage tesla micro-mixers is four, and the number of the collection channels is four.
Preferably, the gas channel includes a first gas channel and a second gas channel, the first gas channel is distributed in a tree shape, the second gas channel is communicated with the tail end of the first gas channel, and the second gas channel corresponds to the through groove of the middle chip.
Preferably, the first gas channel is a three-stage tree-shaped channel, the tail end of the three-stage tree-shaped channel is composed of four branch channels, the number of the second gas channels is four, and the four branch channels are respectively communicated with the four second gas channels.
Preferably, one side of the upper chip is provided with a first channel, the cross section of the first channel is L-shaped, one end of the first channel penetrates through the side wall of the upper chip, the other end of the first channel is communicated with the front end channel of the three-stage tree-shaped channel, and the other end of the first channel penetrates through the lower surface of the upper chip.
Preferably, one end of the first outlet channel is communicated with the collecting channel, and the other end of the first outlet channel is communicated with the outer wall of the lower chip.
Has the advantages that: skin cell metabolites can be collected from the outer wall of the lower chip, and the influence of the drug on the skin cells can be monitored in real time through the skin cell metabolites.
Preferably, the channel depth of the tesla micromixer is less than the thickness of the lower chip.
Preferably, the depths of the first inlet channel, the first main channel, the second main channel, the collecting channel and the first outlet channel are less than the thickness of the lower chip.
Preferably, the depth of the gas channel is smaller than the thickness of the upper chip.
Preferably, the upper chip is fixed with the middle chip and the lower chip through screws.
Preferably, the second gas passages, the through grooves and the collecting passage are identical in shape.
Preferably, the porous membrane is a PES membrane or a PVDF membrane.
The working principle of the invention is as follows: covering the porous membrane on the collecting channel, then putting the middle chip, putting the prepared skin tissue into the through groove, and finally putting the upper chip. When in operation, the medicines with different concentrations enter the first main channel from different first inlet channels, because the depressed Tesla micro-mixers are arranged in parallel, and the first inlet channels are all positioned at the middle parts of the adjacent Tesla micro-mixers, the medicines in the adjacent first inlet channels can enter the depressed channels of the Tesla micro-mixers between the adjacent first inlet channels simultaneously after being mixed, when the number of the Tesla micro-mixers is two, the Tesla micro-mixers only contain the medicines with one concentration, when the number of the Tesla micro-mixers is at least three, the medicines with different concentrations in the Tesla micro-mixers on the non-two sides simultaneously flow in and are quickly and efficiently mixed by the Tesla micro-mixers to form the medicines with stable concentration gradient, then the medicines enter the collecting channel through the channel outlets of the plurality of Tesla micro-mixers, because the lower surface of the porous membrane covers on the collecting channel, the medicine passes through the porous membrane to be supplied to skin tissues, meanwhile, gas is introduced from the gas channel, the gas introduced into the gas channel generates gas flow to the skin tissues in the through groove due to the fact that the sunken gas channel corresponds to the through groove, a gas-liquid phase culture environment is provided for the skin tissues, skin tissue metabolites penetrate through the porous membrane to enter the medicine, and after substance exchange, the skin tissue metabolites flow into the first outlet channel from the collecting channel.
The invention has the advantages that: the drug test bionic skin chip provided by the invention can provide a gas-liquid phase culture environment for skin culture, realize bionic gas-liquid phase skin tissue culture and better simulate a human body microenvironment;
the bionic skin chip for testing the medicine has a simple structure, and can quickly and efficiently mix the medicine by adopting the Tesla micro-mixer, so that a stable medicine concentration gradient is formed, and the efficiency and the reliability of the medicine test are improved.
The skin tissue metabolites in the first outlet channel can be collected and monitored in real time, thereby monitoring the influence of different concentration gradient drugs on the skin tissue.
Drawings
FIG. 1 is an exploded view of a drug testing biomimetic skin chip in example 1 of the present invention;
FIG. 2 is an exploded perspective view of a drug testing biomimetic skin chip in example 1 of the present invention;
FIG. 3 is a perspective view of an upper chip in embodiment 1 of the present invention;
fig. 4 is a bottom view of the upper chip in embodiment 1 of the present invention;
FIG. 5 is a perspective view of a middle layer chip in example 1 of the present invention;
FIG. 6 is a top view of a lower chip in example 1 of the present invention;
FIG. 7 shows the detection of different concentrations H by using the bionic skin chip for drug testing in example 1 in example 2 of the present invention2O2A graph of the effect on skin cell survival;
in the figure: an upper chip 11; a first gas passage 12; a second gas passage 13; a first channel 14; a middle layer chip 21; a through groove 22; a porous membrane 31; a lower chip 41; a first inlet passage 42; a first main channel 43; a first stage tesla micromixer 44; a second main channel 45; a second stage tesla micromixer 46; a collecting channel 47; a first outlet passage 48; a second channel 49.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It will be understood that when an element is referred to as being "secured to" another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present.
It is noted that, in this document, relational terms such as first and second, and the like, if any, are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other identical elements in a process, method, article, or apparatus that comprises the element.
Example 1
The utility model provides a bionic skin chip of medicine test, as shown in fig. 1 and fig. 2, includes upper chip 11, middle level chip 21, porous membrane 31 and lower floor's chip 41 that from the top down set gradually, and for easy to assemble, upper chip 11 upper surface is equipped with the screw hole that runs through, and middle level chip 21 and lower floor's chip 41 surface are equipped with corresponding screw hole, pass through screwed connection between upper chip 11, middle level chip 21 and the lower floor's chip 41.
As shown in fig. 2, 3 and 4, the bottom surface of the upper chip 11 is provided with an upwardly recessed gas channel, the gas channel includes a first gas channel 12 and a second gas channel 13, the first gas channel 12 is in tree-shaped distribution, in this embodiment, the first gas channel 12 is a three-stage tree-shaped channel, the end of the three-stage tree-shaped channel is formed by four branch channels, the number of the second gas channels 13 is four, and the four branch channels at the end of the three-stage tree-shaped channel are respectively communicated with the four second gas channels 13.
In order to facilitate the gas to enter the gas channel, a first channel 14 is arranged on one side of the upper chip 11, the cross section of the first channel 14 is L-shaped, one end of the first channel 14 penetrates through the side wall of the upper chip 11 and is communicated with the front end channel of the three-stage tree-shaped channel, and the other end of the first channel 14 penetrates through the lower surface of the upper chip 11.
As shown in fig. 1, 2 and 6, the bottom surface of the lower chip 41 is provided with a downward-recessed Tesla micro mixer, a downward-recessed first inlet channel 42, a downward-recessed first main channel 43, a downward-recessed collecting channel 47 and a downward-recessed first outlet channel 48, the Tesla micro mixer is formed by a Tesla (Tesla) structure, the Tesla micro mixer is a prior art, and the fluid is caused to flow back by using Coanda effect, so that chaotic convection can be greatly enhanced, and the mixing effect can be improved, and the depths of the Tesla micro mixer, the downward-recessed first inlet channel 42, the downward-recessed first main channel 43, the downward-recessed collecting channel 47 and the downward-recessed first outlet channel 48 are all smaller than the thickness of the lower chip 41.
In order to form more substance concentration gradients, the Tesla micro-mixers are composed of multiple stages, the multiple stages of Tesla micro-mixers are sequentially connected in series, an outlet channel of any one Tesla micro-mixer in the front stage is positioned in the middle of an inlet channel of an adjacent Tesla micro-mixer in the rear stage, the number of the Tesla micro-mixers in the rear stage is one more than that of the Tesla micro-mixers in the front stage, and the size of each stage of Tesla micro-mixer is the same.
The tesla micro-mixer in this embodiment is composed of two stages, including a first stage tesla micro-mixer 44 and a second stage tesla micro-mixer 46, where the number of the first stage tesla micro-mixers 44 is three, the number of the second stage tesla micro-mixers 46 is four, and the number of the first inlet channels 42 is two.
The channel inlets of the three first stage tesla micro-mixers 44 are all communicated with the side wall of the first main channel 43, wherein the channel inlets of the two first stage tesla micro-mixers 44 are respectively communicated with two ends of the side wall of the first main channel 43, the channel inlet of the other first stage tesla micro-mixer 44 is positioned in the middle of the side wall of the first main channel 43, the first inlet channel 42 is respectively positioned in the middle of the adjacent first stage tesla micro-mixer 44, one end of the first inlet channel 42 is communicated with the side wall of the first main channel 43, and the axis of the first stage tesla micro-mixer 44 in this embodiment is perpendicular to the axis of the first main channel 43.
The channel inlets of the four second stage tesla micro-mixers 46 are all communicated with the side wall of the second main channel 45, the channel inlets of the four second stage tesla micro-mixers 46 are evenly distributed on the second main channel 45, wherein the channel inlets of the two second stage tesla micro-mixers 46 are respectively communicated with the side wall of the second main channel 45, the channel outlets of the three first stage tesla micro-mixers 44 are respectively positioned between the channel inlets of the adjacent second stage tesla micro-mixers 46, and the channel outlets of the first stage tesla micro-mixers 44 are communicated with the side wall of the second main channel 45.
The channel outlets of the second stage tesla micro-mixer 46 are communicated with the collecting channels 47, the number of the collecting channels 47 is four, one end of each collecting channel 47 is communicated with the channel outlet of the second stage tesla micro-mixer 46, the other end of each collecting channel 47 is communicated with one end of a first outlet channel 48, and the other end of each first outlet channel 48 is communicated with the outer wall of the lower chip 41.
In order to facilitate the drug entering the first inlet channel 42, a second channel 49 is disposed on one side of the lower chip 41, in this embodiment, the second channel 49 has an L-shaped cross-section, one end of the second channel 49 penetrates through the side wall of the lower chip 41, the other end of the second channel 49 penetrates through the upper surface of the lower chip 41, and the other end of the second channel 49 is communicated with the first inlet channel 42.
As shown in fig. 1, 2 and 5, the surface of the middle layer chip 21 is provided with through grooves 22 corresponding to the second gas channels 13, and the number of the through grooves 22 in the present embodiment is four.
The upper surface of the porous membrane 31 covers below the through slot 22, the lower surface of the porous membrane 31 covers above the collecting channel 47, and the lower surface of the porous membrane 31 is attached to the upper surface of the collecting channel 47.
In order to make the porous membrane 31 better fit under the through grooves 22 and the lower surface of the collecting channel 47 and make the gas flow on the surface of the skin tissue better, the shape of the second gas channel 13, the shape of the through grooves 22 and the shape and the size of the collecting channel 47 are the same in the embodiment.
The working principle of the embodiment is as follows: the porous membrane 31 is covered on the collecting channel 47, then the middle chip 21 is placed, the prepared skin tissue is placed in the through groove 22, finally the upper chip 11 is placed, and then the upper chip 11, the middle chip 21 and the lower chip 41 are fixed through screws.
During operation, the drugs with different concentrations enter the first inlet channel 42 from the inlets of the two second channels 49, pass through the first main channel 43, because the first inlet channel 42 is positioned between the two adjacent first stage tesla micromixers 44, because the recessed tesla micromixers are arranged in parallel, and the first inlet channel 42 is positioned in the middle of the adjacent first stage tesla micromixers 44, the drugs with the same concentration enter the two adjacent first stage tesla micromixers 44, the middle first stage tesla micromixer 44 has two drugs with different concentrations flowing into and mixing, the drug concentration in the first stage tesla micromixers 44 at the two sides is unchanged, the drugs in the first stage tesla micromixer 44 enter the second main channel 45, flow into the second stage tesla micromixer 46 from the second main channel 45, are mixed by the second stage tesla micromixer 46, four drug concentration gradients are formed and then respectively flow into the collecting channel 47 from the channel outlet of the second stage Tesla micro-mixer 46 to be collected, as the lower surface of the porous membrane 31 covers the collecting channel 47, the drugs pass through the porous membrane 31 to be supplied to skin tissues, meanwhile, gas is introduced from the gas channel, as the sunken gas channel corresponds to the through groove 22, the gas introduced in the gas channel generates gas flow to the skin tissues in the through groove 22 to provide a gas-liquid phase culture environment for the skin tissues, and metabolites of the skin tissues enter the drugs through the porous membrane 31 and flow into the first outlet channel 48 from the collecting channel 47 after the substances are exchanged.
If the drugs with the concentration of 0 and 2mol/L are respectively introduced from the inlet of the first inlet channel 42 and are mixed by the three first-stage Tesla micro-mixers 44, the drug concentration at the outlet of the channel of the first-stage Tesla micro-mixer 44 is respectively 0, 1mol/L and 2mol/L, and the drug concentration at the outlet of the channel of the second-stage Tesla micro-mixer 46 is respectively 0, 0.5mol/L, 1.5mol/L and 2mol/L after being mixed by the second-stage Tesla micro-mixer 46, four drugs with different concentration gradients are formed.
In this embodiment, the width dimensions of the first gas channel 12, the second gas channel 13, the first channel 14, the first inlet channel 42, the first main channel 43, the first stage tesla micromixer 44, the second main channel 45, the second stage tesla micromixer 46, the collecting channel 47, and the first outlet channel 48 are in the microscale range (within millimeter), so that the fluid forms a laminar flow.
The beneficial effects of the embodiment are that: the drug test bionic skin chip provided by the invention can provide a gas-liquid phase culture environment for skin culture, realize bionic gas-liquid phase skin tissue culture and better simulate a human body microenvironment;
the bionic skin chip for testing the medicine has a simple structure, and can quickly and efficiently mix the medicine by adopting the Tesla micro-mixer, so that a stable medicine concentration gradient is formed, and the efficiency and the reliability of the medicine test are improved.
The skin tissue metabolites in the first outlet channel 48 can be collected and monitored in real time to monitor the effect of different gradient concentrations of the drug on the skin tissue.
Example 2
H was detected using the drug test biomimetic skin chip of example 12O2The damage to skin cells is effected by placing prepared skin tissue into the channel 22 and introducing H at concentrations of 0% and 0.2% from the inlet of the second channel 492O2After 24 hours of administration, cell survival in cell culture chambers was examined (FIG. 7), indicating H2O2A stable concentration gradient is formed and cell viability decreases with increasing drug concentration.
The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. A drug testing bionic skin chip is characterized in that: comprises an upper chip, a middle chip, a porous membrane and a lower chip which are arranged in sequence from top to bottom;
the bottom surface of the upper layer chip is provided with a sunken gas channel, and the middle layer chip is provided with a through groove corresponding to the gas channel;
the upper surface of the lower chip is provided with at least three sunken Tesla micro-mixers, a first inlet channel, a first main channel, a collecting channel and a first outlet channel, the Tesla micro-mixers are arranged in parallel, channel inlets of the Tesla micro-mixers are connected with the first main channel, the first inlet channels are positioned in the middle of the adjacent Tesla micro-mixers, one end of each first inlet channel is communicated with the first main channel, channel outlets of the Tesla micro-mixers are communicated with the collecting channel, and the first outlet channels are communicated with the collecting channel;
the upper surface of the porous membrane covers below the through grooves, and the lower surface of the porous membrane covers on the collecting channel.
2. The drug testing biomimetic skin chip of claim 1, wherein: the Tesla micro-mixers comprise a plurality of stages of Tesla micro-mixers which are sequentially connected in series, an outlet channel of any one Tesla micro-mixer of the front stage is positioned in the middle of an inlet channel of an adjacent Tesla micro-mixer of the rear stage, and the number of the Tesla micro-mixers of the rear stage is one more than that of the Tesla micro-mixers of the front stage.
3. The drug testing biomimetic skin chip of claim 2, wherein: the multistage Tesla micro-mixer comprises a first stage Tesla micro-mixer and a second stage Tesla micro-mixer; the channel inlets of the first stage Tesla micro-mixers are connected with a first main channel, and the first inlet channels are positioned in the middle of the adjacent first stage Tesla micro-mixers;
the channel inlet of the second stage Tesla micro-mixer is provided with a second main channel, the channel inlet of the second stage Tesla micro-mixer is communicated with the second main channel, the channel outlet of the first stage Tesla micro-mixer is positioned in the middle of the adjacent second stage Tesla micro-mixer, and the channel outlet of the second stage Tesla micro-mixer is communicated with the collecting channel.
4. The drug testing biomimetic skin chip of claim 3, wherein: the number of the first stage tesla micro-mixers is three, the number of the second stage tesla micro-mixers is four, and the number of the collecting channels is four.
5. The drug testing biomimetic skin chip of claim 1, wherein: the gas channel comprises a first gas channel and a second gas channel, the first gas channel is in tree-shaped distribution, the second gas channel is communicated with the tail end of the first gas channel, and the second gas channel corresponds to the through groove of the middle chip.
6. The drug testing biomimetic skin chip of claim 5, wherein: the first gas channel is a three-stage tree-shaped channel, the tail end of the three-stage tree-shaped channel is composed of four branch channels, the number of the second gas channels is four, and the four branch channels are respectively communicated with the four second gas channels.
7. The drug testing biomimetic skin chip of claim 6, wherein: one side of upper chip is equipped with first passageway, the cross-section of first passageway is L shape, the front end passageway intercommunication of the lateral wall of upper chip, the other end of first passageway and tertiary arborescent passageway is passed to one end of first passageway, the other end of first passageway runs through the lower surface of upper chip.
8. The drug testing biomimetic skin chip of claim 1, wherein: one end of the first outlet channel is communicated with the collecting channel, and the other end of the first outlet channel is communicated with the outer wall of the lower chip.
9. The drug testing biomimetic skin chip of claim 1, wherein: the depth of the channel of the Tesla micro-mixer is smaller than the thickness of the lower chip.
10. The drug testing biomimetic skin chip of claim 1, wherein: the depths of the first inlet channel, the first main channel, the second main channel, the collecting channel and the first outlet channel are less than the thickness of the lower chip.
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CN112755867A (en) * | 2020-12-17 | 2021-05-07 | 广东省医疗器械研究所 | Micro-mixing chip and micro-mixing device |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN204097450U (en) * | 2014-05-21 | 2015-01-14 | 大连医科大学 | A kind of multidimensional many concentration susceptibility detects micro-fluidic chip |
WO2019183998A1 (en) * | 2018-03-28 | 2019-10-03 | 东南大学 | Micro-flow control chip for cell tissue culture and real-time monitoring, and use method therefor |
CN110408542A (en) * | 2019-08-22 | 2019-11-05 | 合肥学院 | A kind of skin chip of liquid phase culture |
-
2020
- 2020-04-28 CN CN202010350146.4A patent/CN111349564A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN204097450U (en) * | 2014-05-21 | 2015-01-14 | 大连医科大学 | A kind of multidimensional many concentration susceptibility detects micro-fluidic chip |
WO2019183998A1 (en) * | 2018-03-28 | 2019-10-03 | 东南大学 | Micro-flow control chip for cell tissue culture and real-time monitoring, and use method therefor |
CN110408542A (en) * | 2019-08-22 | 2019-11-05 | 合肥学院 | A kind of skin chip of liquid phase culture |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112755867A (en) * | 2020-12-17 | 2021-05-07 | 广东省医疗器械研究所 | Micro-mixing chip and micro-mixing device |
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