CN114317267B - Multi-layer microfluidic organ chip with multi-stage alveolar tube structure and manufacturing method thereof - Google Patents
Multi-layer microfluidic organ chip with multi-stage alveolar tube structure and manufacturing method thereof Download PDFInfo
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Abstract
The invention discloses a multi-layer microfluidic organ chip with a multi-stage alveolar tube structure and a manufacturing method thereof. The lung organ chip mainly comprises three parts: a microfluidic pipeline chip layer, an intermediate thin film chip layer and a pressure chamber chip layer; wherein the microfluidic channel chip layer and the pressure chamber chip layer are positioned on the upper side and the lower side of the middle film chip layer. The device is used for researching the fluid flow characteristics and aerosol deposition rules of the alveolar region of the respiratory tract in the respiratory tract of a human body, has simple operation principle, can accurately control the flow rate of inlet fluid entering an upper-layer microfluidic pipeline, and improves the accuracy of research.
Description
Technical Field
The invention belongs to the field of microfluidic organ chips, and particularly relates to a multi-layer microfluidic organ chip with a multi-stage alveolar tube structure and a manufacturing method thereof.
Background
Human survival is closely related to the atmosphere. In recent years, with the development of economy, the quality of the atmospheric environment gradually deteriorates. The haze caused by air pollution is not only extremely harmful to human bodies, but also damages the environmental protection and the sustainable development of cities. Research finds that PM in the atmosphere 2.5 It is possible to greatly increase the probability that a person suffers from various respiratory diseases. The complex flow in the deep lung of the human body and the transportation rule of micro-nano particles are researched, so that the method can help us to better understand the invasion process of harmful aerosol in the environment to the human body and the transmission mechanism of aerosol medicine in the lung.
Currently, there are two main types of alveolar experimental models: an enlarged alveolar experimental model and a true size experimental model. The structure of the enlarged alveolus model is enlarged proportionally, so that flow and measurement are conveniently displayed, but the structure of the enlarged model is simpler, for example, only a single alveolus or an alveolus approximated by a ring is researched, so that important characteristics of alveolar respiratory flow cannot be reproduced on a real scale. The real-size experimental model is mainly manufactured by processing a microfluidic chip. Currently, researchers have designed single-stage alveolar canal models and multi-stage alveolar canal models, respectively. However, the single-stage alveolar pipe model cannot truly reveal the systematicness of fluid and particle transportation, and the structure designed by the multi-stage alveolar pipe model is not well matched with the real situation of a human body in size, so that the whole research is inaccurate.
Disclosure of Invention
The invention aims at overcoming the defects of the prior art and provides a multi-layer microfluidic organ chip with a multi-stage alveolar tube structure and a manufacturing method thereof. The invention has simple principle, convenient operation and repeated use. The multistage alveolar tracheobronchial tree structure can reproduce the systematicness of fluid and particle transportation, and the channel size is designed according to the alveolar tracheobronchial tree structure in a human body, so that the research accuracy is improved.
The aim of the invention is realized by the following technical scheme: a multi-layer microfluidic organ chip having a multi-stage alveolar tube structure, comprising:
the microfluidic pipeline chip layer comprises a fluid main channel, a simulated multistage alveolar pipe structure microchannel, a transition microchannel, an alveolar sac structure and a microfluidic pipeline fluid access channel, wherein the fluid main channel, the simulated multistage alveolar pipe structure microchannel, the transition microchannel and the alveolar sac structure are communicated, the fluid main channel comprises a fluid main channel access and exit, the side wall of the simulated multistage alveolar pipe structure microchannel is provided with a plurality of alveolar structures with different sizes and structures, and the transition microchannel and the alveolar sac structure comprise a terminal alveolar transition microchannel and a terminal alveolar sac structure;
a pressure chamber chip layer; the microfluidic channel comprises a pressure chamber, wherein the pressure chamber is provided with a pressure chamber fluid inlet and outlet channel, and a chamber collapse preventing supporting structure is arranged in the pressure chamber;
the middle film chip layer is a deformable single-layer elastic film and is provided with a middle film fluid access channel, and the middle film fluid access channel is communicated with the microfluidic pipeline fluid access channel of the microfluidic pipeline chip layer at the corresponding position and the pressure chamber fluid access channel of the pressure chamber chip layer; and
the microfluidic pipeline chip layer, the middle film chip layer and the pressure chamber chip layer are assembled and connected in sequence from top to bottom.
Further, the fluid main channel of the microfluidic channel chip layer is a rectangular cross-section channel, the length of the fluid main channel is 10mm, and the cross-section dimension perpendicular to the fluid flow direction is 667 μm×400 μm.
Further, the simulated multistage alveolar pipe of the microfluidic pipeline chip layer has a five-stage tree-shaped pipeline structure, each stage is a rectangular section pipeline, and the first stage alveolar pipe is communicated with the fluid main channel;
the tail end of each level of alveolar pipe extends and branches into two symmetrical secondary alveolar pipes at a certain angle, and five levels integrally form a tree structure;
the bifurcation angle from the primary alveolar pipe to the secondary alveolar pipe is 120 degrees; the bifurcation angle of the second-stage alveolar ducts to the third-stage alveolar ducts is 80 °; the bifurcation angle of the third level alveolar pipe to the fourth level alveolar pipe is 60 degrees; the bifurcation angle of the fourth-stage alveolar pipe to the fifth-stage alveolar pipe is 60 degrees;
the total length of the channels of the first-stage alveolar pipe is 1330um, and the cross-sectional dimension perpendicular to the fluid flow direction is 667 mu m multiplied by 400 mu m; the total length of the channels of the second-stage alveolar pipes is 1120um, and the cross-sectional dimension perpendicular to the fluid flow direction is 632 mu m multiplied by 400 mu m; the total length of the channels of the third-stage alveolar pipe is 930um, and the cross-sectional dimension perpendicular to the fluid flow direction is 400 mu m multiplied by 400 mu m; the total length of the channels of the fourth-stage alveolus tube is 830um, and the cross section dimension perpendicular to the fluid flow direction is 362 mu m multiplied by 400 mu m; the total length of the channels of the fifth-stage alveolar pipes is 700um, and the cross-sectional dimension perpendicular to the fluid flow direction is 327 mu m multiplied by 400 mu m.
Further, the side walls of each stage of alveolar-pipe micro-channel are provided with an alveolar structure, the channel height at the alveoli is 150um, the diameter of the first stage of alveoli is 110um, the diameter of the second stage of alveoli is 115um, the diameter of the third stage of alveoli is 165um, the diameter of the fourth stage of alveoli is 175um, the diameter of the fifth stage of alveoli is 185um, and the half open angle of each stage of alveoli is 60 degrees.
Further, the side walls of the micro-channels of the alveolar ducts of each stage are additionally provided with alveoli with different sizes, and the diameters of the alveoli are respectively 100um, 140um and 180um;
the side walls of the micro-channels of the alveolar pipes of each stage are additionally provided with alveoli with different half-open angles, and the half-open angles of the alveoli are respectively 45 degrees, 75 degrees and 90 degrees.
Further, the side wall of the fifth-stage alveolar-canal microchannel is additionally provided with four groups of alveoli with the circular center distance smaller than 1 time of the alveolar diameter, the alveolar diameters are 180um, the half open angles are 60 degrees, and the circular center distances are 97.5um, 115.625um, 138.75m and 161.875um respectively.
Further, the fifth level alveolar duct microchannel communicates with the terminal alveolar transition microchannel, the terminal alveolar duct transition microchannel is a rectangular section pipeline, the lengths of the transition microchannels at different positions are slightly different and are approximately 6500um, the cross-sectional dimensions of the channels perpendicular to the fluid flow direction are 327 um×400um, the terminal alveolar duct transition microchannel communicates with the terminal alveolar structure, and the diameter of the terminal alveolar is 2.5mm and the height is 400um.
Further, the thickness of the middle film chip layer is 50um, the elastic modulus is 1.7MPa, and the micro-channel of the micro-flow pipeline chip layer and the micro-channel of the pressure chamber chip layer are positioned on the upper side and the lower side of the middle film chip layer.
Further, the height of the pressure chamber is 1mm, the left and right parts of the support structure for preventing the chamber from collapsing are symmetrical and are in a fan shape, the small arc radius of the fan shape is 4.5mm, the large arc radius is 8.5mm, the fan-shaped central angle is 150 degrees, and the depth of the support structure for preventing the chamber from collapsing is 1mm and is the same as the height of the pressure chamber.
A method of fabricating a multi-layered microfluidic organ chip having a multi-stage alveolar structure according to any one of claims 1 to 9, comprising the steps of:
firstly, pouring a microfluidic pipeline chip layer with a fluid main channel, a simulated multistage alveolar structure microchannel, a terminal alveolar sac transition microchannel and a terminal alveolar structure and a pressure chamber chip layer with a pressure chamber by using PDMS; and sequentially bonding the micro-flow pipeline chip layer, the middle film chip layer and the pressure chamber chip layer from top to bottom, wherein the micro-channels of the micro-flow pipeline chip layer and the micro-channels of the pressure chamber chip layer are positioned on the upper side and the lower side of the middle film chip layer, so that the complete multi-layer micro-fluidic organ chip with the multi-stage alveolar pipe structure is obtained.
The multilayer microfluidic organ chip provided by the embodiment of the invention has at least the following beneficial effects: the multilayer microfluidic organ chip has the advantages of simple principle, convenient operation and repeated use. The inlet fluid flow rate into the upper microfluidic channel can be precisely controlled by connecting the pressure chambers to a pressure control device to periodically reciprocate the fluid within the multi-stage alveolar microfluidic channel, and periodically deforming the membrane layer to simulate the expansion and contraction movements of the alveoli and alveolar ducts. The multistage alveolar tracheobronchial tree structure can reproduce the systematicness of fluid and particle transportation, and the channel size is designed according to the alveolar tracheobronchial tree structure in a human body, so that the research accuracy is improved.
Drawings
FIG. 1 is a schematic diagram of the overall structure of a multi-layer microfluidic organ chip according to an embodiment of the invention;
FIG. 2 is a schematic diagram of a microchannel structure of a simulated multistage alveolar structure of a microfluidic pipeline chip layer according to an embodiment of the present invention.
Detailed Description
The invention will be described in further detail with reference to the drawings and the specific examples.
As shown in fig. 1, the present invention provides a multi-layered microfluidic organ chip having a multi-stage alveolar-pipe structure, comprising: a microfluidic pipeline chip layer 1, an intermediate thin film chip layer 2 and a pressure chamber chip layer 3.
The microfluidic pipeline chip layer 1 comprises a fluid main channel 11, a simulated multistage alveolar pipe structure microchannel 12, a transition microchannel, an alveolar sac structure 13 and a microfluidic pipeline fluid access channel 14, wherein the fluid main channel 11, the simulated multistage alveolar pipe structure microchannel 12, the transition microchannel and the alveolar sac structure 13 are communicated; the main fluid channel 11 is used for flowing working fluid, the main fluid channel 11 comprises a main fluid channel inlet and outlet 111 and a main fluid channel main body 112, and the side wall of the micro-channel 12 simulating the multistage alveolar structure is provided with a plurality of alveolar structures with different sizes and structures, and the transition micro-channel and alveolar sac structure 13 comprises a terminal alveolar transition micro-channel 131 and a terminal alveolar sac structure 132.
The microfluidic channel of the pressure chamber chip layer 3 comprises a pressure chamber 31, a pressure chamber fluid inlet and outlet channel 33 is arranged on the pressure chamber 31, and a chamber collapse preventing supporting structure 32 is arranged in the pressure chamber 31.
The middle film chip layer 2 is a deformable single-layer elastic film and is provided with a middle film fluid inlet and outlet channel 21, and the middle film fluid inlet and outlet channel 21 is communicated with the corresponding micro-flow pipeline fluid inlet and outlet channel 14 of the micro-flow pipeline chip layer 1 and the pressure chamber fluid inlet and outlet channel 33 of the pressure chamber chip layer 3.
The pressure chamber fluid inlet and outlet channel 33 is in a semicircular structure, the middle film fluid inlet and outlet channel 21 is a circular channel, and the projection of the center of the cross section of the two channels on the horizontal plane is coincident.
The microfluidic channel fluid inlet and outlet channel 14 and the intermediate film fluid inlet and outlet channel 21 are circular channels, and the projections of the centers of the cross sections of the two channels on the horizontal plane are coincident. The microfluidic channel fluid inlet/outlet channel 14 is located on the axis symmetry line of the main fluid channel body 112, and is spaced apart from the center of the circle of the fluid inlet/outlet 111 by 30mm.
The axis of symmetry of the main fluid channel body 112 at the microfluidic channel chip layer 1 coincides with the projection of the axis of symmetry of the pressure chambers 31 at the pressure chamber chip layer 3 onto a horizontal plane.
The microfluidic pipeline chip layer 1, the middle film chip layer 2 and the pressure chamber chip 3 are assembled and connected in sequence from top to bottom.
In one embodiment, the fluid main channel 112 of the microfluidic channel chip layer 1 is a rectangular cross-section channel, the length of the fluid main channel 112 is 10mm and the cross-sectional dimension perpendicular to the fluid flow direction is 667 μm×400 μm.
As shown in fig. 2, in one embodiment, the simulated multi-stage alveolar pipe of the microfluidic pipeline chip layer 1 has a five-stage tree-like pipeline structure, each stage is a rectangular-section pipeline, wherein the first-stage alveolar pipe 121 is communicated with the main fluid channel body 112 in the main fluid channel 11;
the tail end of each level of alveolar pipe extends and branches into two symmetrical secondary alveolar pipes at a certain angle, and five levels integrally form a tree structure;
the bifurcation angle of the first stage alveolar pipe 121 to the second stage alveolar pipe 122 is 120 °; the bifurcation angle of the second stage alveolar pipe 122 to the third stage alveolar pipe 123 was 80 °; the bifurcation angle of the third stage alveolar pipe 123 to the fourth stage alveolar pipe 124 is 60 °; the angle of bifurcation of the fourth stage alveolar ducts to the fifth stage alveolar ducts was 60 °.
As shown in FIG. 2, in one embodiment, the primary to fifth alveolar pipe structure sizes are each designed based on the size of the 16-20 th order real alveolar pipe of the human lung. The total length of the channels of the first-stage alveolar pipe 121 is 1330um, and the cross-sectional dimension perpendicular to the fluid flow direction is 667 μm (width, the same applies hereinafter) x 400 μm (height, the same applies hereinafter); the total length of the channels of the second stage alveolar tube 122 is 1120um, and the cross-sectional dimension perpendicular to the fluid flow direction is 632 μm×400 μm; the total length of the channels of third stage alveolar pipe 123 is 930um, and the cross-sectional dimension perpendicular to the fluid flow direction is 400 μm×400 μm; the total length of the channels of the fourth stage alveolar tube 124 is 830um, and the cross-sectional dimensions perpendicular to the fluid flow direction are 362 μm×400 μm; the total length of the channels of the fifth stage alveolar ducts 125 is 700um and the cross-sectional dimensions perpendicular to the fluid flow direction are 327 μm x 400 μm.
As shown in FIG. 2, in one embodiment, each stage of alveolar-pipe micro-channel has an alveolar structure on its sidewall, the channel height at the alveoli is 150um, the diameter of the first stage of alveoli is 110um, the diameter of the second stage of alveoli is 115um, the diameter of the third stage of alveoli is 165um, the diameter of the fourth stage of alveoli is 175um, the diameter of the fifth stage of alveoli is 185um, and the half-open angle of each stage of alveoli is 60 °.
In one embodiment, as shown in FIG. 2, the side walls of each stage of alveolar-canal microchannel are additionally provided with alveoli of different sizes for experimental comparison. Such alveoli have diameters of 100um, 140um and 180um, respectively;
the side walls of each stage of alveolar duct micro-channel are additionally provided with alveoli with different half open angles, and the alveoli are used for experimental comparison. The half-angles of such alveoli are 45 °, 75 ° and 90 °.
In one embodiment, as shown in FIG. 2, the side walls of the fifth class alveolar-canal microchannel 125 are further provided with four groups of alveoli with a circular center distance of less than 1 time of the alveolar diameter, and two alveoli are used as a group for experimental comparison. Such alveoli are 180um in diameter and 60 ° in half-open angle, and as shown in fig. 2, the circular center distance of the alveoli 1253 is 97.5um (0.5 times diameter), the circular center distance of the alveoli 1252 is 115.625um (0.75 times diameter), the circular center distance of the alveoli 1254 is 138.75m (0.875 times diameter), and the circular center distance of the alveoli 1255 is 161.875um (0.95 times diameter).
In one embodiment, as shown in FIG. 2, fifth stage alveolar-tube microchannel 125 communicates with terminal alveolar-sac transition microchannel 131. The transition micro-channel 131 of the end vesicle is a rectangular section pipeline, and the lengths of the transition micro-channels at different positions are slightly different, and the length is about 6500 um. The cross-sectional dimensions of the channels perpendicular to the fluid flow direction were 327 μm by 400 μm. The three-level tracheal tree at the tail end of the human lung has a large number of alveolar structures to form an alveolar sac with a complex structure, and the alveolar sac is simplified into an independent circular chamber by the physical model. In this embodiment, the terminal alveolar sac transition microchannel 131 is in structural communication with terminal alveolar sacs 132, the diameter of terminal alveolar sacs 132 being 2.5mm and the height being 400um.
Based on the real alveolar canal and the anatomical dimension design of the alveoli of the human body, the flow field and particle deposition are researched through the experimental model, the systematicness of fluid and particle transportation can be reappeared, and further the invasion process of harmful aerosol in the environment to the human body and the transmission mechanism of aerosol medicine in the lung can be better understood.
As shown in fig. 1, in an embodiment, the thickness of the middle thin film chip layer is 50um, the elastic modulus is 1.7MPa, and the micro-channels of the micro-flow pipeline chip layer and the micro-channels of the pressure chamber chip layer are located on the upper side and the lower side of the middle thin film chip layer.
As shown in FIG. 1, in one embodiment, the height of the pressure chamber is 1mm, the left and right parts of the support structure for preventing the chamber from collapsing are symmetrical, and the support structure is in a fan shape, the small arc radius of the fan shape is 4.5mm, the large arc radius is 8.5mm, the central angle of the fan shape is 150 degrees, and the depth of the support structure for preventing the chamber from collapsing is 1mm and is the same as the height of the pressure chamber.
In one embodiment, microfluidic channel chip layer 1 and pressure chamber chip layer 3 are typically formed by casting, etc. fluid main channel 11, simulated multi-stage alveolar structure microchannel 12, terminal alveolar sac transition microchannel 13, terminal alveolar sac structure 14 and pressure chamber 31 using a flexible material such as PDMS as a substrate. The middle film chip layer 2 is usually obtained by spin coating a flexible material such as PDMS.
In one embodiment, a method for fabricating a multi-layer microfluidic organ chip having a multi-stage alveolar-tube structure is provided, comprising the steps of: firstly, pouring a micro-flow pipeline chip layer 1 with a fluid main channel 11, a simulated multistage alveolar structure micro-channel 12 and a tail end alveolar sac transition micro-channel 13, wherein the micro-flow pipeline chip layer 1 with a tail end alveolar sac structure 14 and a pressure chamber chip layer 3 with a pressure chamber 31 by using PDMS; and then sequentially bonding the micro-flow pipeline chip layer 1, the middle film chip layer 2 and the pressure chamber chip layer 3 from top to bottom, wherein the micro-channels of the micro-flow pipeline chip layer 1 and the micro-channels of the pressure chamber chip layer 3 are positioned on the upper side and the lower side of the middle film chip layer 2, so as to obtain the complete micro-flow control chip.
The multi-layer microfluidic organ chip has simple principle, and the pressure chamber is connected with the pressure control device to enable the fluid in the multi-stage alveolus microfluidic pipeline to periodically reciprocate, so that the film layer periodically deforms to simulate the expansion and contraction movements of alveoli and alveolus tubes, thereby accurately controlling the flow rate of inlet fluid entering the upper-layer microfluidic pipeline.
By means of the multilayer microfluidic organ chip, the deposition distribution situation that particles sucked into the chip can enter alveolar ducts and alveoli can be counted in a real situation, so that the transportation and deposition characteristics of PM2.5 particles in the alveolar ducts and alveoli are studied; in addition, the chip can also guide the research of medicines so as to improve the efficiency of delivering medicines to lesion positions or improve the transportation efficiency of magnetic targeting medicines; furthermore, alveolar cells can be planted in the multilayer microfluidic organ chip, the physiological characteristics of the alveolar cells can be studied, and toxicity screening of medicines can be performed.
The multilayer microfluidic organ chip and the manufacturing method thereof have at least the following beneficial effects: the multilayer microfluidic organ chip has the advantages of simple principle, convenient operation and repeated use. The inlet fluid flow rate into the upper microfluidic channel can be precisely controlled by connecting the pressure chambers to a pressure control device to periodically reciprocate the fluid within the multi-stage alveolar microfluidic channel, and periodically deforming the membrane layer to simulate the expansion and contraction movements of the alveoli and alveolar ducts. The multistage alveolar tracheobronchial tree structure can reproduce the systematicness of fluid and particle transportation, and the channel size is designed according to the alveolar tracheobronchial tree structure in a human body, so that the research accuracy is improved.
The embodiments of the present invention have been described in detail with reference to the accompanying drawings, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge of one of ordinary skill in the art without departing from the spirit of the present invention. Furthermore, embodiments of the invention and features of the embodiments may be combined with each other without conflict.
Claims (8)
1. A multi-layer microfluidic organ chip having a multi-stage alveolar-tube structure, comprising:
the microfluidic pipeline chip layer comprises a fluid main channel, a simulated multistage alveolar pipe structure microchannel, a transition microchannel, an alveolar sac structure and a microfluidic pipeline fluid access channel, wherein the fluid main channel, the simulated multistage alveolar pipe structure microchannel, the transition microchannel and the alveolar sac structure are communicated, the fluid main channel comprises a fluid main channel access and exit, the side wall of the simulated multistage alveolar pipe structure microchannel is provided with a plurality of alveolar structures with different sizes and structures, and the transition microchannel and the alveolar sac structure comprise a terminal alveolar transition microchannel and a terminal alveolar sac structure;
a pressure chamber chip layer; the microfluidic channel comprises a pressure chamber, wherein the pressure chamber is provided with a pressure chamber fluid inlet and outlet channel, and a chamber collapse preventing supporting structure is arranged in the pressure chamber;
the middle film chip layer is a deformable single-layer elastic film and is provided with a middle film fluid access channel, and the middle film fluid access channel is communicated with the microfluidic pipeline fluid access channel of the microfluidic pipeline chip layer at the corresponding position and the pressure chamber fluid access channel of the pressure chamber chip layer; and
the microfluidic pipeline chip layer, the middle film chip layer and the pressure chamber chip layer are assembled and connected in sequence from top to bottom;
the simulated multistage alveolar pipe of the microfluidic pipeline chip layer has a five-stage tree-shaped pipeline structure, each stage is a rectangular section pipeline, and the first stage alveolar pipe is communicated with the fluid main channel;
the tail end of each level of alveolar pipe extends and branches into two symmetrical secondary alveolar pipes at a certain angle, and five levels integrally form a tree structure;
the bifurcation angle from the primary alveolar pipe to the secondary alveolar pipe is 120 degrees; the bifurcation angle of the second-stage alveolar ducts to the third-stage alveolar ducts is 80 °; the bifurcation angle of the third level alveolar pipe to the fourth level alveolar pipe is 60 degrees; the bifurcation angle of the fourth-stage alveolar pipe to the fifth-stage alveolar pipe is 60 degrees;
the total length of the channels of the first-stage alveolar pipe is 1330um, and the cross-sectional dimension perpendicular to the fluid flow direction is 667 mu m multiplied by 400 mu m; the total length of the channels of the second-stage alveolar pipes is 1120um, and the cross-sectional dimension perpendicular to the fluid flow direction is 632 mu m multiplied by 400 mu m; the total length of the channels of the third-stage alveolar pipe is 930um, and the cross-sectional dimension perpendicular to the fluid flow direction is 400 mu m multiplied by 400 mu m; the total length of the channels of the fourth-stage alveolus tube is 830um, and the cross section dimension perpendicular to the fluid flow direction is 362 mu m multiplied by 400 mu m; the total length of the channels of the fifth-stage alveolar pipe is 700um, and the cross-sectional dimension perpendicular to the fluid flow direction is 327 mu m multiplied by 400 mu m;
the side walls of each stage of alveolar-pipe micro-channel are provided with an alveolar structure, the channel height at the alveoli is 150um, the diameter of the first stage of alveoli is 110um, the diameter of the second stage of alveoli is 115um, the diameter of the third stage of alveoli is 165um, the diameter of the fourth stage of alveoli is 175um, the diameter of the fifth stage of alveoli is 185um, and the half open angle of each stage of alveoli is 60 degrees.
2. The multi-layered microfluidic organ chip with multi-stage alveolar-tube structure according to claim 1, wherein the fluid main channel of the microfluidic channel chip layer is a rectangular cross-section channel having a length of 10mm and a cross-sectional dimension perpendicular to the fluid flow direction of 667 μm x 400 μm.
3. The multi-layer microfluidic organ chip with multi-stage alveolar-tube structure according to claim 1, wherein the sidewalls of the alveolar-tube microchannels of each stage are additionally provided with alveoli with different sizes, and the diameters of the alveoli are 100um, 140um and 180um respectively;
the side walls of the micro-channels of the alveolar pipes of each stage are additionally provided with alveoli with different half-open angles, and the half-open angles of the alveoli are respectively 45 degrees, 75 degrees and 90 degrees.
4. The multi-stage alveolar-pipe structured multi-layer microfluidic organ chip according to claim 1, wherein the side walls of the fifth-stage alveolar-pipe micro-channel are additionally provided with four groups of alveoli with circular center distances smaller than 1 time of alveolar diameter, the alveolar diameters are 180um, the half open angles are 60 degrees, and the circular center distances are 97.5um, 115.625um, 138.75m and 161.875um respectively.
5. The multi-layered microfluidic organ chip according to claim 1, wherein the fifth level alveolar tube microchannel is in communication with the terminal alveolar transition microchannel, the terminal alveolar transition microchannel is a rectangular cross-section channel, the transition microchannel at different positions has a slightly different length and a length of approximately 6500um, the cross-sectional dimension of the channel perpendicular to the fluid flow direction is 327 μm x 400 μm, the terminal alveolar sac transition microchannel is in communication with the terminal alveolar sac structure, and the diameter of the terminal alveolar sac is 2.5mm and the height is 400um.
6. The multi-layered microfluidic organ chip with multi-stage alveolar-tube structure according to claim 1, wherein the thickness of the middle thin film chip layer is 50um and the elastic modulus is 1.7MPa, and the micro-channels of the microfluidic channel chip layer and the micro-channels of the pressure chamber chip layer are located at the upper and lower sides of the middle thin film chip layer.
7. The multi-layer microfluidic organ chip with multi-stage alveolar tube structure according to claim 1, wherein the height of the pressure chamber is 1mm, the left and right parts of the chamber collapse prevention support structure are symmetrical and are in a fan shape, the small arc radius of the fan shape is 4.5mm, the large arc radius is 8.5mm, the central angle of the fan shape is 150 degrees, and the depth of the chamber collapse prevention support structure is 1mm and is the same as the height of the pressure chamber.
8. A method of fabricating a multi-layered microfluidic organ chip having a multi-stage alveolar structure according to any one of claims 1 to 7, comprising the steps of:
firstly, pouring a microfluidic pipeline chip layer with a fluid main channel, a simulated multistage alveolar structure microchannel, a terminal alveolar sac transition microchannel and a terminal alveolar structure and a pressure chamber chip layer with a pressure chamber by using PDMS; and sequentially bonding the micro-flow pipeline chip layer, the middle film chip layer and the pressure chamber chip layer from top to bottom, wherein the micro-channels of the micro-flow pipeline chip layer and the micro-channels of the pressure chamber chip layer are positioned on the upper side and the lower side of the middle film chip layer, so that the complete multi-layer micro-fluidic organ chip with the multi-stage alveolar pipe structure is obtained.
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| CN202210006089.7A CN114317267B (en) | 2022-01-05 | 2022-01-05 | Multi-layer microfluidic organ chip with multi-stage alveolar tube structure and manufacturing method thereof |
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| CN202210006089.7A CN114317267B (en) | 2022-01-05 | 2022-01-05 | Multi-layer microfluidic organ chip with multi-stage alveolar tube structure and manufacturing method thereof |
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| CN112574884A (en) * | 2020-11-19 | 2021-03-30 | 深圳先进技术研究院 | Multifunctional organ chip based on microfluidic technology, preparation method and application thereof |
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| CN112574884A (en) * | 2020-11-19 | 2021-03-30 | 深圳先进技术研究院 | Multifunctional organ chip based on microfluidic technology, preparation method and application thereof |
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