CN114317267A - Multilayer microfluidic organ chip with multistage alveolar tube structure and manufacturing method thereof - Google Patents
Multilayer microfluidic organ chip with multistage alveolar tube structure and manufacturing method thereof Download PDFInfo
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Abstract
The invention discloses a multilayer microfluidic organ chip with a multistage alveolar tube structure and a manufacturing method thereof. The lung organ chip mainly comprises three parts: a microfluidic pipeline chip layer, a middle film chip layer and a pressure chamber chip layer; wherein the microflow pipeline chip layer and the pressure chamber chip layer are positioned at the upper side and the lower side of the middle film chip layer. The device is used for researching the fluid flow characteristics and the aerosol deposition rule of the respiratory tract alveolar region in the human respiratory tract, has a simple operation principle, can accurately control the flow rate of the inlet fluid entering the upper-layer microflow pipeline, and improves the research accuracy.
Description
Technical Field
The invention belongs to the field of microfluidic organ chips, and particularly relates to a multilayer microfluidic organ chip with a multistage alveolar tube structure and a manufacturing method thereof.
Background
Human survival is closely related to the atmosphere. With the development of economy in recent years, the quality of the atmospheric environment is gradually deteriorated. Haze caused by air pollution is not only extremely harmful to human bodies, but also harms environmental protection and sustainable development of cities. Studies have found that PM in the atmosphere2.5It is possible to greatly increase the probability of a person suffering from various respiratory diseases. The study on the complex flow in the deep lung of the human body and the transportation rule of micro-nano particles can help us to better understand the harmful aerosol in the environment to the human bodyThe invasive process of (a) and the mechanism of transport of aerosol drugs in the lungs.
At present, there are two main experimental models of alveoli: enlarging alveolus experimental model and real size experimental model. The amplified alveolar model amplifies the structure in proportion, so that the flow and measurement are conveniently displayed, but the amplified alveolar model has a simpler structure, and important characteristics of alveolar respiratory flow cannot be reproduced on a real scale if only a single alveolar or an annularly approximate alveolar is researched. The real-size experimental model is mainly manufactured by processing a micro-fluidic chip. Currently, researchers have designed single-stage alveolar pipe models and multi-stage alveolar pipe models respectively. However, the above 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 good in size in accordance with the real condition of a human body, so that the overall research is inaccurate.
Disclosure of Invention
The invention aims to provide a multilayer microfluidic organ chip with a multistage alveolar tube structure and a manufacturing method thereof, aiming at the defects of the prior art. The invention has simple principle, convenient operation and repeated use. The multistage alveolar tracheal tree structure can reproduce the systematicness of fluid and particle transportation, and the size of the channel is designed according to the alveolar tracheal tree structure in a human body, so that the research accuracy is improved.
The purpose of the invention is realized by the following technical scheme: a multi-layered microfluidic organ chip having a multi-stage alveolar tube structure, comprising:
the microfluidic pipeline chip layer comprises a main fluid channel, a simulated multistage alveolar tube structure microchannel, a transition microchannel, a alveolar sac structure and a microfluidic pipeline fluid inlet and outlet channel, wherein the main fluid channel, the simulated multistage alveolar tube structure microchannel, the transition microchannel and alveolar sac structure are communicated with each other, the main fluid channel comprises a main fluid channel inlet and outlet, a plurality of alveolar structures with different sizes and structures are arranged on the side wall of the simulated multistage alveolar tube structure microchannel, and the transition microchannel and alveolar sac structure comprises a terminal alveolar sac transition microchannel and a terminal alveolar sac structure;
a pressure chamber chip layer; the microfluidic channel comprises a pressure chamber, a pressure chamber fluid inlet and outlet channel is arranged on the pressure chamber, and a chamber collapse prevention supporting structure is arranged in the pressure chamber;
the middle thin film chip layer is a deformable single-layer elastic thin film and is provided with a middle thin film fluid inlet and outlet channel, and the middle thin film fluid inlet and outlet channel is communicated with the micro-flow pipeline fluid inlet and outlet channel of the micro-flow pipeline chip layer at the corresponding position and the pressure chamber fluid inlet and outlet channel of the pressure chamber chip layer; and
the microflow pipeline chip layer, the middle thin film chip layer and the pressure chamber chip layer are sequentially assembled and connected from top to bottom.
Further, the main fluid channel of the microfluidic channel chip layer is a rectangular cross-section channel, the length of the main fluid channel is 10mm, and the cross-sectional dimension perpendicular to the fluid flow direction is 667 μm × 400 μm.
Furthermore, the simulated multistage alveolar ducts of the microfluidic pipeline chip layer have a five-stage tree-shaped pipeline structure, each stage is a pipeline with a rectangular section, and the first stage alveolar duct is communicated with the fluid main channel;
the tail end of each stage of alveolar pipe extends and bifurcates into two symmetrical secondary alveolar pipes according to a certain angle, and a tree-shaped structure is integrally formed by five stages;
the bifurcation angle from the first stage alveolar pipe to the second stage alveolar pipe is 120 degrees; the bifurcation angle from the second-stage alveolar pipe to the third-stage alveolar pipe is 80 degrees; the bifurcation angle from the third stage alveolar pipe to the fourth stage alveolar pipe is 60 degrees; the bifurcation angle from the fourth-stage alveolar pipe to the fifth-stage alveolar pipe is 60 degrees;
the total length of the channel of the first stage alveolar pipe is 1330um, and the cross-sectional dimension perpendicular to the flow direction of the fluid is 667μm multiplied by 400μm; the total length of the channel of the second stage alveolar pipe is 1120um, and the cross-sectional dimension perpendicular to the flow direction of the fluid is 632 mu m multiplied by 400 mu m; the total length of the channel of the third stage alveolar pipe is 930um, and the cross-sectional dimension perpendicular to the flow direction of the fluid is 400 microns multiplied by 400 microns; the total length of the channel of the fourth stage alveolar pipe is 830um, and the cross-sectional dimension perpendicular to the flow direction of the fluid is 362 microns multiplied by 400 microns; the total length of the channel of the fifth stage alveolar pipe is 700um, and the cross-sectional dimension perpendicular to the fluid flow direction is 327 μm × 400 μm.
Furthermore, all have the alveolar structure on each level alveolar pipe microchannel's the lateral wall, alveolus department channel height is 150um, and first order alveolus diameter is 110um, and second order alveolus diameter is 115um, and third order alveolus diameter is 165um, and fourth order alveolus diameter is 175um, and fifth order alveolus diameter is 185um, and the half-open angle of each level alveolus is 60.
Furthermore, the side wall of each stage of alveolar duct microchannel is additionally provided with alveoli with different sizes, and the diameters of the alveoli are respectively 100um, 140um and 180 um;
the side wall of each stage of alveolar duct microchannel is additionally provided with alveoli with different half-opening angles, and the half-opening angles of the alveoli are 45 degrees, 75 degrees and 90 degrees respectively.
Furthermore, four groups of alveoli with the center distance of less than 1 time of the diameter of the alveoli are arranged on the side wall of the fifth stage alveolar pipe microchannel, the diameters of the alveoli are all 180um, the half-open angles are all 60 degrees, and the center distances are respectively 97.5um, 115.625um, 138.75m and 161.875 um.
Further, the fifth stage alveolar duct microchannel is communicated with the end alveolar sac transition microchannel, the end alveolar sac transition microchannel is a rectangular section pipeline, the lengths of the transition microchannels at different positions are slightly different and are approximately 6500um, the section dimension of the channel perpendicular to the fluid flow direction is 327 microns multiplied by 400 microns, the end alveolar sac transition microchannel is communicated with the end alveolar sac structure, the diameter of the end alveolar sac is 2.5mm, and the height of the end alveolar sac is 400 um.
Further, the thickness of middle film chip layer is 50um, and elastic modulus is 1.7MPa, the microchannel of miniflow pipeline chip layer with the microchannel of pressure chamber chip layer is located the upper and lower both sides of middle film chip layer.
Further, the height of the pressure chamber is 1mm, the left part and the right part of the cavity collapse prevention supporting structure are symmetrical and are in a sector ring shape, the radius of a small arc of the sector ring shape is 4.5mm, the radius of a large arc of the sector ring shape is 8.5mm, the central angle of the sector ring shape is 150 degrees, and the depth of the cavity collapse prevention supporting structure is 1mm and is the same as the height of the pressure chamber.
A method for manufacturing a multilayer microfluidic organ chip with a multistage alveolar tube structure according to any one of claims 1 to 9, comprising the steps of:
firstly, pouring a micro-flow pipeline chip layer with a fluid main channel, a simulated multistage alveolar pipe structure micro-channel, a tail end alveolar sac transition micro-channel and a tail end alveolar sac structure and a pressure chamber chip layer with a pressure chamber by using PDMS; and then bonding the microfluidic pipeline chip layer, the middle film chip layer and the pressure chamber chip layer from top to bottom in sequence, wherein the micro-channel of the microfluidic 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, so as to obtain the complete multilayer microfluidic organ chip with the multistage alveolar tube structure.
The multilayer microfluidic organ chip provided by the embodiment of the invention at least has the following beneficial effects: the multilayer microfluidic organ chip has simple principle and convenient operation, and can be used repeatedly. The pressure chamber is connected with the pressure control device to enable the fluid in the multistage alveolar microflow pipeline to periodically reciprocate, so that the thin film layer is periodically deformed to simulate the expansion and contraction movement of alveoli and alveolar ducts, and the flow rate of the fluid entering the inlet of the upper layer microflow pipeline can be accurately controlled. The multistage alveolar tracheal tree structure can reproduce the systematicness of fluid and particle transportation, and the size of the channel is designed according to the alveolar tracheal 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 present invention;
FIG. 2 is a schematic diagram of a simulated multi-stage alveolar-tubular microchannel structure of a microfluidic channel chip layer according to an embodiment of the present invention.
Detailed Description
The invention is described in further detail below with reference to the figures and specific examples.
As shown in fig. 1, the present invention provides a multi-layered microfluidic organ chip having a multi-stage alveolar tube structure, comprising: a microflow pipeline chip layer 1, a middle film chip layer 2 and a pressure chamber chip layer 3.
The microfluidic pipeline chip layer 1 comprises a main fluid channel 11, a simulated multistage alveolar tube structure microchannel 12, a transition microchannel and alveolar sac structure 13 and a microfluidic pipeline fluid inlet and outlet channel 14, wherein the main fluid channel 11, the simulated multistage alveolar tube structure microchannel 12, the transition microchannel and alveolar sac structure 13 are communicated with each other; the main fluid channel 11 is used for flowing working fluid, the main fluid channel 11 includes a main fluid channel inlet 111 and a main fluid channel body 112, the side wall of the microchannel 12 simulating the multistage alveolar pipe structure has a plurality of alveolar structures with different sizes and structures, and the transition microchannel and alveolar structure 13 includes a terminal alveolar transition microchannel 131 and a terminal alveolar 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 prevention support structure 32 is arranged in the pressure chamber 31.
The middle thin film chip layer 2 is a deformable single-layer elastic thin film and is provided with a middle thin film fluid inlet and outlet channel 21, and the middle thin film fluid inlet and outlet channel 21 is communicated with the 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 at corresponding positions.
The pressure chamber fluid inlet and outlet channel 33 is of a semicircular structure, the middle film fluid inlet and outlet channel 21 is a circular channel, and the projections of the circle centers of the cross sections of the two channels on the horizontal plane are overlapped.
The microfluidic pipeline fluid inlet and outlet channel 14 and the middle membrane fluid inlet and outlet channel 21 are both circular channels, and the projections of the circle centers of the cross sections of the two channels on the horizontal plane are coincident. The microfluidic pipeline fluid inlet and outlet channel 14 is located on the axial symmetry line of the main channel body 112 and is located 30mm away from the center of the fluid inlet and outlet 111.
The axial symmetry line of the main fluid channel body 112 in the microfluidic channel chip layer 1 coincides with the projection of the axial symmetry line of the pressure chambers 31 in the pressure chamber chip layer 3 on the horizontal plane.
The microflow pipeline chip layer 1, the middle film chip layer 2 and the pressure chamber chip 3 are sequentially assembled and connected from top to bottom.
In one embodiment, the main fluid channel 112 of the microfluidic channel chip layer 1 is a rectangular cross-section channel, and the main fluid channel 112 has a length of 10mm and a cross-sectional dimension perpendicular to the direction of fluid flow of 667 μm × 400 μm.
As shown in fig. 2, in one embodiment, the simulated multi-stage alveolar pipe of the microfluidic chip layer 1 has a five-stage tree-shaped 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 stage of alveolar pipe extends and bifurcates into two symmetrical secondary alveolar pipes according to a certain angle, and a tree-shaped structure is integrally formed by five stages;
the bifurcation angle from the first stage alveolar tube 121 to the second stage alveolar tube 122 is 120 °; the bifurcation angle from the second stage alveolar duct 122 to the third stage alveolar duct 123 is 80 °; the bifurcation angle from the third alveolar 123 to the fourth alveolar 124 is 60 °; the bifurcation angle from the fourth stage alveolar pipe to the fifth stage alveolar pipe is 60 degrees.
As shown in FIG. 2, in one embodiment, the first through fifth stage alveolar duct structures are each sized based on the size of the 16 th-20 th stage true alveolar duct of a human lung. The first stage alveolar duct 121 has a total channel length of 1330um and a cross-sectional dimension perpendicular to the flow direction of the fluid of 667 μm (width, hereinafter the same) x 400 μm (height, hereinafter the same); the total channel length 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 channel of the third stage alveolar duct 123 is 930um, and the cross-sectional dimension perpendicular to the fluid flow direction is 400 μm × 400 μm; the fourth stage alveolar duct 124 has a total channel length of 830um and a cross-sectional dimension perpendicular to the fluid flow direction of 362 μm × 400 μm; the fifth stage alveolar tube 125 has a total channel length of 700um and cross-sectional dimensions perpendicular to the flow direction of the fluid of 327 μm × 400 μm.
As shown in FIG. 2, in one embodiment, the alveolar ducts of the respective stages have alveolar structures on the sidewalls, the height of the alveolar ducts is 150 μm, the diameter of the first stage alveoli is 110 μm, the diameter of the second stage alveoli is 115 μm, the diameter of the third stage alveoli is 165 μm, the diameter of the fourth stage alveoli is 175 μm, the diameter of the fifth stage alveoli is 185 μm, and the half-open angles of the alveoli are all 60 °.
As shown in FIG. 2, in one embodiment, the alveolar ducts of different sizes are further provided on the side walls of the microchannels for experimental comparison. Such alveoli are 100um, 140um and 180um in diameter, respectively;
the side wall of each stage of alveolar canal microchannel is additionally provided with alveoli with different half-open angles for experimental comparison. The half-open angles of such alveoli are 45 °, 75 ° and 90 °, respectively.
In one embodiment, as shown in fig. 2, four groups of alveoli with a center distance smaller than 1 times the diameter of the alveoli are disposed on the side wall of the fifth stage alveolar duct microchannel 125, and two alveoli are used as a group for experimental comparison. Such alveoli are all 180um in diameter and 60 ° in half-open angle, as shown in fig. 2, the centre distance of the alveoli 1253 group is 97.5um (0.5 times diameter), the centre distance of the alveoli 1252 group is 115.625um (0.75 times diameter), the centre distance of the alveoli 1254 group is 138.75m (0.875 times diameter), and the centre distance of the alveoli 1255 group is 161.875um (0.95 times diameter).
In one embodiment, as shown in fig. 2, the fifth stage alveolar duct microchannel 125 communicates with the terminal alveolar transition microchannel 131. The end alveolar sac transition micro-channel 131 is a rectangular section pipeline, and the lengths of transition micro-channels at different positions are slightly different, and the length is about 6500 um. The cross-sectional dimension of the channel perpendicular to the fluid flow direction is 327 μm 400 μm. The tail-most three-level tracheal tree of the human lung has a large number of alveolar structures to form a alveolar sac with a complex structure, and the alveolar sac is simplified into an independent circular cavity by the physical model. In this embodiment, the terminal alveolar transition microchannel 131 is in structural communication with a terminal alveolar sac 132, and the terminal alveolar sac 132 has a diameter of 2.5mm and a height of 400 um.
The experimental model is used for researching flow field and particle deposition based on the anatomical dimension design of the real alveolar ducts and alveoli of the human body, so that the systematicness of fluid and particle transportation can be reproduced, and the invasion process of harmful aerosol in the environment to the human body and the transmission mechanism of aerosol medicines 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 microchannels of the microfluidic channel chip layer and the microchannels of the pressure chamber chip layer are located at the upper and lower sides of the middle thin film chip layer.
As shown in fig. 1, in an 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 are in a fan-shaped ring shape, the radius of a small arc of the fan-shaped ring is 4.5mm, the radius of a large arc of the fan-shaped ring is 8.5mm, the central angle of the fan-shaped ring is 150 °, 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, the microfluidic channel chip layer 1 and the pressure chamber chip layer 3 are formed by casting a main fluid channel 11, a microchannel 12 simulating a multistage alveolar tube structure, a terminal alveolar sac transition microchannel 13, a terminal alveolar sac structure 14 and a pressure chamber 31, which are usually made of a flexible material such as PDMS. The intermediate thin film chip layer 2 can be generally obtained by spin coating a material with certain flexibility, such as PDMS.
In one embodiment, a method for manufacturing a multilayer microfluidic organ chip with a multistage alveolar tube structure is provided, which comprises the following steps: firstly, pouring a micro-fluidic pipeline chip layer 1 with a fluid main channel 11, a simulated multistage alveolar pipe structure micro-channel 12, a tail end alveolar sac transition micro-channel 13 and 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-channel of the micro-flow pipeline chip layer 1 and the micro-channel of the pressure chamber chip layer 3 are positioned at the upper side and the lower side of the middle film chip layer 2, so as to obtain the complete micro-flow pipeline chip.
The multilayer microfluidic organ chip has a simple principle, and can make fluid in a multistage alveolar microfluidic pipeline periodically reciprocate by connecting the pressure chamber with the pressure control device, so that the thin film layer is periodically deformed to simulate the expansion and contraction motions of the alveoli and the alveolar ducts, and the flow rate of fluid entering the inlet of the upper microfluidic pipeline can be accurately controlled.
By means of the multilayer microfluidic organ chip, the deposition distribution condition that particulate matters sucked into the chip can enter alveolar ducts and alveoli can be counted under a real condition, so that the transport and deposition characteristics of PM2.5 particles in the alveolar ducts and the alveoli can be researched; in addition, the chip can also guide the research of the medicine so as to improve the efficiency of conveying the medicine to the pathological change position or improve the transportation efficiency of the magnetic targeting medicine; furthermore, alveolar cells can be planted in the multilayer microfluidic organ chip to study the physiological characteristics of the alveolar cells and carry out toxicity screening of medicines.
The multilayer microfluidic organ chip and the manufacturing method thereof provided by the embodiment of the invention at least have the following beneficial effects: the multilayer microfluidic organ chip has simple principle and convenient operation, and can be used repeatedly. The pressure chamber is connected with the pressure control device to enable the fluid in the multistage alveolar microflow pipeline to periodically reciprocate, so that the thin film layer is periodically deformed to simulate the expansion and contraction movement of alveoli and alveolar ducts, and the flow rate of the fluid entering the inlet of the upper layer microflow pipeline can be accurately controlled. The multistage alveolar tracheal tree structure can reproduce the systematicness of fluid and particle transportation, and the size of the channel is designed according to the alveolar tracheal 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 those skilled in the art without departing from the gist of the present invention. Furthermore, the embodiments of the present invention and the features of the embodiments may be combined with each other without conflict.
Claims (10)
1. A multi-layered microfluidic organ chip having a multi-stage alveolar tube structure, comprising:
the microfluidic pipeline chip layer comprises a main fluid channel, a simulated multistage alveolar tube structure microchannel, a transition microchannel, a alveolar sac structure and a microfluidic pipeline fluid inlet and outlet channel, wherein the main fluid channel, the simulated multistage alveolar tube structure microchannel, the transition microchannel and alveolar sac structure are communicated with each other, the main fluid channel comprises a main fluid channel inlet and outlet, a plurality of alveolar structures with different sizes and structures are arranged on the side wall of the simulated multistage alveolar tube structure microchannel, and the transition microchannel and alveolar sac structure comprises a terminal alveolar sac transition microchannel and a terminal alveolar sac structure;
a pressure chamber chip layer; the microfluidic channel comprises a pressure chamber, a pressure chamber fluid inlet and outlet channel is arranged on the pressure chamber, and a chamber collapse prevention supporting structure is arranged in the pressure chamber;
the middle thin film chip layer is a deformable single-layer elastic thin film and is provided with a middle thin film fluid inlet and outlet channel, and the middle thin film fluid inlet and outlet channel is communicated with the micro-flow pipeline fluid inlet and outlet channel of the micro-flow pipeline chip layer at the corresponding position and the pressure chamber fluid inlet and outlet channel of the pressure chamber chip layer; and
the microflow pipeline chip layer, the middle thin film chip layer and the pressure chamber chip layer are sequentially assembled and connected from top to bottom.
2. The multi-layered microfluidic organ chip with the multistage alveolar-tube structure according to claim 1, wherein the main fluid channel of the microfluidic channel chip layer is a rectangular-section channel, the length of the main fluid channel is 10mm, and the cross-sectional dimension perpendicular to the fluid flow direction is 667 μm x 400 μm.
3. The multi-layer microfluidic organ chip with the multi-stage alveolar tube structure according to claim 1, wherein the simulated multi-stage alveolar tubes of the microfluidic channel chip layer have a five-stage tree-shaped pipeline structure, each stage is a rectangular-section pipeline, and a first-stage alveolar tube is communicated with the main fluid channel;
the tail end of each stage of alveolar pipe extends and bifurcates into two symmetrical secondary alveolar pipes according to a certain angle, and a tree-shaped structure is integrally formed by five stages;
the bifurcation angle from the first stage alveolar pipe to the second stage alveolar pipe is 120 degrees; the bifurcation angle from the second-stage alveolar pipe to the third-stage alveolar pipe is 80 degrees; the bifurcation angle from the third stage alveolar pipe to the fourth stage alveolar pipe is 60 degrees; the bifurcation angle from the fourth-stage alveolar pipe to the fifth-stage alveolar pipe is 60 degrees;
the total length of the channel of the first stage alveolar pipe is 1330um, and the cross-sectional dimension perpendicular to the flow direction of the fluid is 667μm multiplied by 400μm; the total length of the channel of the second stage alveolar pipe is 1120um, and the cross-sectional dimension perpendicular to the flow direction of the fluid is 632 mu m multiplied by 400 mu m; the total length of the channel of the third stage alveolar pipe is 930um, and the cross-sectional dimension perpendicular to the flow direction of the fluid is 400 microns multiplied by 400 microns; the total length of the channel of the fourth stage alveolar pipe is 830um, and the cross-sectional dimension perpendicular to the flow direction of the fluid is 362 microns multiplied by 400 microns; the total length of the channel of the fifth stage alveolar pipe is 700um, and the cross-sectional dimension perpendicular to the fluid flow direction is 327 μm × 400 μm.
4. The multi-layer microfluidic organ chip with the multi-stage alveolar tube structure according to claim 3, wherein the alveolar structures are arranged on the side walls of the alveolar tube microchannels of each stage, the heights of the alveoli are all 150 μm, the diameters of the first stage alveoli are 110 μm, the diameters of the second stage alveoli are 115 μm, the diameters of the third stage alveoli are 165 μm, the diameters of the fourth stage alveoli are 175 μm, the diameters of the fifth stage alveoli are 185 μm, and the half-open angles of the alveoli of each stage are 60 °.
5. The multi-layer microfluidic organ chip with the multi-stage alveolar tube structure according to claim 3, wherein the side walls of the alveolar tube microchannels of each stage are additionally provided with alveoli with different sizes, and the diameters of the alveoli are respectively 100um, 140um and 180 um;
the side wall of each stage of alveolar duct microchannel is additionally provided with alveoli with different half-opening angles, and the half-opening angles of the alveoli are 45 degrees, 75 degrees and 90 degrees respectively.
6. The multi-layered microfluidic organ chip with a multistage alveolar tube structure according to claim 3, wherein the side wall of the fifth-stage alveolar tube microchannel is further provided with four groups of alveoli with a center distance of less than 1 times the diameter of the alveoli, the diameters of the alveoli are 180um, the half-open angles are 60 degrees, and the center distances are 97.5um, 115.625um, 138.75m and 161.875um respectively.
7. The multi-layered microfluidic organ chip with a multi-stage alveolar tube structure according to claim 3, wherein the fifth stage alveolar tube microchannel is communicated with the terminal alveolar sac transition microchannel, the terminal alveolar sac transition microchannel is a rectangular cross-section pipeline, the lengths of the transition microchannels at different positions are slightly different and are 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 communicated with the terminal alveolar sac structure, and the diameter of the terminal alveolar sac is 2.5mm and the height of the terminal alveolar sac is 400 um.
8. The multi-layered microfluidic organ chip with the multistage alveolar tube structure according to claim 1, wherein the thickness of the middle thin film chip layer is 50um, the elastic modulus is 1.7MPa, and the microchannels of the microfluidic channel chip layer and the microchannels of the pressure chamber chip layer are located at upper and lower sides of the middle thin film chip layer.
9. The multi-layer microfluidic organ chip with the multi-stage alveolar tube structure according to claim 1, wherein the pressure chamber has a height of 1mm, the left and right parts of the support structure for preventing chamber collapse are symmetrical and have a fan-shaped ring shape, the radius of the small arc of the fan-shaped ring shape is 4.5mm, the radius of the large arc of the fan-shaped ring shape is 8.5mm, the central angle of the fan-shaped ring shape is 150 °, and the depth of the support structure for preventing chamber collapse is 1mm and is the same as the height of the pressure chamber.
10. A method for manufacturing a multilayer microfluidic organ chip with a multistage alveolar tube structure according to any one of claims 1 to 9, comprising the steps of:
firstly, pouring a micro-flow pipeline chip layer with a fluid main channel, a simulated multistage alveolar pipe structure micro-channel, a tail end alveolar sac transition micro-channel and a tail end alveolar sac structure and a pressure chamber chip layer with a pressure chamber by using PDMS; and then bonding the microfluidic pipeline chip layer, the middle film chip layer and the pressure chamber chip layer from top to bottom in sequence, wherein the micro-channel of the microfluidic 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, so as to obtain the complete multilayer microfluidic organ chip with the multistage alveolar tube structure.
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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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| US20200160752A1 (en) * | 2018-11-19 | 2020-05-21 | National Tsing Hua University | Imitating lung device, system for simulating human lung, method for simulating human breathing, system for simulating deposition of substance in human lung and method of the same |
| CN111489624A (en) * | 2020-04-30 | 2020-08-04 | 哈尔滨工业大学(深圳)(哈尔滨工业大学深圳科技创新研究院) | Single-alveolus three-dimensional amplification model and alveolus respiration simulation device |
| 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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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20200160752A1 (en) * | 2018-11-19 | 2020-05-21 | National Tsing Hua University | Imitating lung device, system for simulating human lung, method for simulating human breathing, system for simulating deposition of substance in human lung and method of the same |
| CN111489624A (en) * | 2020-04-30 | 2020-08-04 | 哈尔滨工业大学(深圳)(哈尔滨工业大学深圳科技创新研究院) | Single-alveolus three-dimensional amplification model and alveolus respiration simulation device |
| 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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