CN103146573A - Artery blood vessel simulation microfluidic device and use thereof - Google Patents
Artery blood vessel simulation microfluidic device and use thereof Download PDFInfo
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Abstract
The invention provides an artery blood vessel simulation microfluidic device and a use thereof. The artery blood vessel simulation microfluidic device comprises a transparent microfluidic channel module and a transparent negative pressure production module matching with the transparent microfluidic channel module. The bottom of the transparent microfluidic channel module and the top of the transparent negative pressure production module are composed of elastic membranes. The bottom of the transparent microfluidic channel module is in a linkage relationship with the top of the transparent negative pressure production module. The transparent microfluidic channel module is used for fluid flowing. The transparent negative pressure production module is used for negative pressure production. The artery blood vessel simulation microfluidic device can be used in fields of artery blood vessel physiological and pathological mechanism study, drug screening or preparation of a kit for biological detection. The artery blood vessel simulation microfluidic device is designed based on a microfluidic technology, combines the transparent microfluidic channel module, the elastic membranes and the transparent negative pressure production module by a reasonable design, provides flow shear stress and mechanical tensile force, builds an atherosclerosis in-vitro study model, provides an effective tool for correlational studies, can be made, used and observed easily, and realizes in-situ dynamic monitoring under the conditions of two types of mechanical stimulation, and chemical stimulation.
Description
Technical field
The present invention relates to a kind of arteries simulation micro fluidic device and application thereof, belong to the biological medicine technology field.
Background technology
The abnormal blood flow kinetic factor is one of crucial risk factor caused cardiovascular and cerebrovascular diseases, but its mechanism of action it be unclear that, and the limitation of traditional research method has hindered Developments.In recent years, the foundation of the outer research model of vascular bodies and application have promoted the progress of correlative study greatly.The kind that produces mechanical stimulation when the haemodynamics in vitro study model of blood vessel can be flowed through blood vessel according to they simulate blood is divided three classes, i.e. hydrodynamic shear model, stretching stress model, hydrodynamic shear and stretching stress interaction model.The hydrodynamic shear model is mainly to adopt the laminar flow plate, and liquid applies fluid shear stress by liquid-inlet and the outlet that is opened on both sides to the cell that is planted in substrate; The stretching stress model applies the mechanical stretching stimulation by the deformation of elastica or plate to adhering to superincumbent cell.The first two model can be inquired into the behavior of cell in single mechanical stimulation situation and change, yet, in the residing organism of cell, be a complex environment that multiple mechanical stimulation is arranged, a cardiovascular systems in vitro study model that more approaches internal milieu must be considered the effect of multiple mechanical stimulation to cell.In recent years, people design and have improved some and can apply device (Moore, the J.E. of hydrodynamic shear and stretching stress simultaneously, Burki, E., Suciu, A., Zhao, S.M., Burnier, M., Brunner, H.R.and Meister, J.J. (1994) A Device for Subjecting Vascular Endothelial-Cells to Both Fluid Shear-Stress and Circumferential Cyclic Stretch.Ann Biomed Eng.22,416-422, Qiu, Y.C.and Tarbell, J.M. (2000) Interaction between wall shear stress and circumferential strain affects endothelial cell biochemical production.J Vasc Res.37,147-157, Toda, M., Yamamoto, K., Shimizu, N., Obi, S., Kumagaya, S., Igarashi, T., Kamiya, A.and Ando, J. (2008) Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch.J Biotechnol.133, 239-244), its the most basic principle is exactly to have attached the silicone rubber tube simulated blood vessel of endotheliocyte with inwall, in the situation that keep certain pressure to apply stretching stress by the expansion of tube chamber to the cell adhered in tube chamber, apply shear-stress by washing away to cell of liquid simultaneously.But, the shortcoming of said apparatus also clearly, cell in the bad control of the adhesion of tube wall, can not the behavior under mechanical stimulation carry out Real Time Observation and intervention etc. to cell, these problems are also restricting the progress of correlative study.In recent years, the fast development of microflow control technique provides opportunity for the foundation of numerous disease pathological study model, micro-fluidic chip can provide closer to the microenvironment under physiology, pathological conditions for cell, can mating surface chemistry and soft lithographic technique cell behavior is controlled and is intervened, can also carry out observation and analysis to the behavior variation of cell at cell colony and unicellular two kinds of levels.(the Huh such as Huh, D., Matthews, B.D., Mammoto, A., Montoya-Zavala, M., Hsin, H.Y.and Ingber, D.E. (2010) Reconstituting Organ-Level Lung Functions on a Chip.Science.328, micro fluidic device 1662-1668) adopted can produce hydrodynamic shear and drawing force to the cell be attached on film, its purposes is simulation and research alveolar function, and its manufacture craft is relatively complicated, because film does not have upholder, easily distortion, be difficult for observation of cell form and change procedure under microscope.(the Douville such as Douville, N.J., Zamankhan, P., Tung, Y.C., Li, R., Vaughan, B.L., Tai, C.F., White, J., Christensen, P.J., Grotberg, J.B.and Takayama, S. (2011) Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model.Lab Chip.11, micro fluidic device 609-619) adopted can provide hydrodynamic shear and mechanical stretching force equally, its purposes is also the structure and function of simulation and research alveolar, can form liquid-gas interface, the microenvironment of simulated lung cystencyte.Yet above-mentioned micro fluidic device is only suitable for doing the alveolar model, micro-fluidic vascular pattern there is no bibliographical information.And there is no patent application both at home and abroad for the research model of micro-fluidic blood vessel physiological and pathological mechanism.
Summary of the invention
Therefore, what the objective of the invention is that external model for existing simulation arteries physiological and pathological state has can not provide hydrodynamic shear and two kinds of stimulations of mechanical stretching force simultaneously, what have is unfavorable for dynamic observation and analysis, and the in-vitro simulated device of micro-fluidic blood vessel still belongs to blank deficiency at present, design a kind of micro fluidic device and application thereof that hydrodynamic shear and mechanical stretching force can be provided simultaneously, can build the external model of some physiology, pathomechanism research, for relevant research provides effective tool.For above-mentioned purpose, technical scheme of the present invention is as follows:
On the one hand, the invention provides a kind of arteries simulation micro fluidic device, this device comprises transparent microchannel module and the transparent negative pressure generation module suitable with it, described microchannel module bottom is connected by elastica with negative pressure generation module top, described microchannel module flows for fluid, and described negative pressure generation module is for generation of the negative pressure that makes elastica generation deformation;
Described microchannel module top is provided with fluid intake and fluid outlet, and described fluid intake and fluid outlet be respectively by with fluid intake and the suitable PE pipe of fluid outlet, being connected in the microchannel of microchannel module bottom, and connects with it;
Described negative pressure generation module top is provided with the negative pressure groove, described negative pressure groove is located at the below of microchannel, thereby form the independent space isolated with microchannel, described negative pressure generation module top is provided with a gas circuit opening, and described gas circuit opening is connected with the negative pressure groove by the 2nd PE pipe suitable with it.
Preferably, described negative pressure groove one side also is provided with the negative pressure Buffer Pool connected with it, and described the 2nd PE pipe is connected with the negative pressure groove by the negative pressure Buffer Pool.
Preferably, described negative pressure Buffer Pool connects by a groove and negative pressure groove, and preferably, described the 2nd PE pipe is vertically connected at negative pressure Buffer Pool bottom.
Preferably, surround into a rectangular platform in the middle of described negative pressure groove, be close to described elastica and, corresponding to the described microchannel of its top, between described rectangular platform and elastica, be filled with liquid lubricant, moving mutually for making effect in negative pressure issue looks.
Preferably, described rectangular platform length is 1.5 * 10
4μ m, wide is 1.0 * 10
3μ m described negative pressure generation module top and bottom involution are structure as a whole.
Preferably, described microchannel is the second rectangular structure, and it forms bottom the 3rd, the 4th sidewall and microchannel bottom and microchannel, and described microchannel bottom consists of elastica, and preferably, the length of described the second rectangular parallelepiped is 1.8 * 10
4μ m, wide is 1.5 * 10
3μ m, height is 0.5 * 10
3μ m.
Preferably, the top of described microchannel module and bottom connect into by first, second sidewall the first rectangular structure that horizontal direction connects, and preferably, the length of described the first rectangular parallelepiped is 2.5-3.0 * 10
4μ m, wide 2.0-2.5 * 10
3μ m, height is 3.0-5.0 * 10
3μ m.
Preferably, described microchannel module, negative pressure generation module and elastica are made by polydimethylsiloxane (PDMS) material.
Preferably, described fluid intake and fluid outlet are circular port, and preferably, the diameter of described circular port is 8.0 * 10
2μ m; A described PE pipe is vertically connected at the microchannel of described microchannel module bottom.
Preferably, the top of described negative pressure generation module is rectangle, and this rectangular length is 2.5-3.0 * 10
4μ m, wide is 2.0-2.5 * 10
4μ m, described negative pressure groove is the 3rd rectangular structure, and its cross section is rectangle, and height is 5 * 10
2μ m, wide is 2.5 * 10
2μ m; Described negative pressure Buffer Pool is the cylindrical cavity shape perpendicular to platform area, and the diameter of described cylindrical cavity is 5.0 * 10
3μ m, height is 1.0 * 10
3μ m; Described groove is the 4th rectangular structure, and its length is 3.0 * 10
3μ m, wide is 5 * 10
2μ m, height is 5 * 10
2μ m; Described gas circuit opening is circular port gas circuit opening, and preferably, the diameter of described circular port gas circuit opening is 8.0 * 10
2μ m.
Preferably, described microchannel module and negative pressure generation module length are 2.5-3.0 * 10
4μ m, wide 2.0-2.5 * 10 that are
4μ m, thick 3.0-5.0 * 10 that are
3μ m; Described elastica is long 2.5-3.0 * 10
4μ m, wide 2.0-2.5 * 10
4μ m, thick is 10-100 μ m.
On the other hand, the invention provides the application of a kind of arteries simulation micro fluidic device in arteries physiological and pathological Mechanism Study or drug screening.
Another aspect, the invention provides the application of a kind of arteries simulation micro fluidic device in the test kit for the preparation of biological detection, preferably, and the test kit that described test kit is arteries physiological and pathological Mechanism Study or drug screening.
Again on the one hand, the invention provides a kind of test kit for biological detection, this test kit comprises according to arteries simulation micro fluidic device of the present invention, also comprise detection reagent and damping fluid, preferably, described detection reagent is vasoactive small molecules, cytokine, antibody or the medicine for screening.
Beneficial effect of the present invention is: based on microflow control technique, micro fluidic device by appropriate design and integrated micro flow channel module, elastica, negative pressure generation module, hydrodynamic shear and mechanical stretching force can be provided simultaneously, set up atherosclerosis in vitro study model, for correlative study provides effective tool, volume is little, simple in structure, is easy to make and use; Optically transparent material is made, be easy to the situation in naked eyes or Microscopic observation passage, can between microscope and incubator, change arbitrarily, can realize cell under two kinds of mechanical stimulations and the original position dynamic monitoring under chemical stimulation, the size of two kinds of mechanical stimulations, frequency are adjustable at any time, can change at any time the chemical micro-environment of cell.
The accompanying drawing explanation
Below, describe by reference to the accompanying drawings embodiment of the present invention in detail, wherein:
The structural representation that Fig. 1 is arteries simulation micro fluidic device of the present invention;
The structural representation that Fig. 2 is arteries simulation microfluidic system of the present invention;
Fig. 3 is that described elastica is positioned over the experimental result schematic diagram that arteries simulation micro fluidic device of the present invention (only having the negative pressure generation module) is stretched, in figure, a is the result schematic diagram of the elastica before stretching, and in figure, b is the experimental result schematic diagram of the elastica after stretching;
Fig. 4 stretches separately with the MSC cell and shears separately the experimental result schematic diagram contrasted after Bone Marrow Stromal Stem Cells (MSC) being inputted to arteries simulation micro fluidic device of the present invention, in figure, a is the experimental result schematic diagram that the MSC cell stretches separately, b is the experimental result schematic diagram that the MSC cell is sheared separately, c be the MSC cell in device of the present invention drawn and shear after the experimental result schematic diagram;
Wherein:
1 is the microchannel module, 101 tops that are the microchannel module, 102 bottoms that are the microchannel module, 103 is the first side wall, and 104 is the second sidewall, and 105 is fluid intake, 106 is fluid outlet, 107 is a PE pipe, and 108 is microchannel, and 1081 is that microchannel top, 1082 is that microchannel bottom, 1083 is that the 3rd sidewall, 1084 is the 4th sidewall;
2 is elastica;
3 is the negative pressure generation module, 301 bottoms that are the negative pressure generation module, 302 tops that are the negative pressure generation module, 303 is the negative pressure groove, and 304 is gas flow opening, 303 negative pressure grooves, 305 is the 2nd PE pipe, 306 negative pressure cushion chambers, and 307 is that groove, 308 is rectangular platform;
4 is arteries simulation micro fluidic device; 5 is the cell cultures drive system; 6 is negative pressure generator.
Embodiment
As shown in Figure 1, arteries simulation micro fluidic device 4 of the present invention, this device comprises transparent microchannel module 1 and the transparent negative pressure generation module 3 suitable with it, described microchannel module bottom and negative pressure generation module top are processed covalent bonding by elastica 2 through plasma oxidation, described microchannel module 1, negative pressure generation module 3 and elastica 2 are made by polydimethylsiloxane (PDMS) material, and described springform 2 is long 2.5-3.0 * 10
4μ m, wide 2.0-2.5 * 10
4μ m, thick is the springform 2 of 10-100 μ m, and described microchannel module 1 is for liquid-flow, and described negative pressure generation module 3 is for generation of making elastica 2 that the negative pressure of deformation occur, described microchannel module top 101 and bottom 102 connect into by first, second sidewall 103,104 the first rectangular structure that horizontal direction connects, and the length of described the first rectangular parallelepiped is 2.5-3.0 * 10
4μ m, wide 2.0-2.5 * 10
4μ m, height is 3.0-5.0 * 10
3μ m, described microchannel module is long is 2.5-3.0 * 10
4μ m, wide is 2.0-2.5 * 10
4μ m, thick is 3.0-5.0 * 10
3μ m, described microchannel module top 101 is provided with fluid intake 105 and fluid outlet 106, described fluid intake 105 and fluid outlet 106 are respectively by being vertically connected at the microchannel 108 of microchannel module bottom 102 with fluid intake 105 and the suitable PE pipe 107 of fluid outlet 106, described microchannel 108 is the second rectangular structure, it is by the microchannel top, bottom 1081, the 1082 and the 3rd, the 4th sidewall 1083, 1084 form, and connect with it, described microchannel bottom consists of elastica, the length of described the second rectangular parallelepiped is 1.8 * 10
4μ m, wide is 1.5 * 10
3μ m, height is 5.0 * 10
2μ m, described fluid intake 105 and fluid outlet 106 are circular port, and the diameter of described circular port is 8.0 * 10
2μ m, the bottom 301 of described negative pressure generation module 3 and top 302 involutions are and into a single integrated structure, and it is long 2.5-3.0 * 10 that described negative pressure produces the film piece
4μ m, wide 2.0-2.5 * 10
4μ m, thick is 3.0-5.0 * 10
3the PDMS module of μ m, described negative pressure generation module top 302 is provided with negative pressure groove 303, described negative pressure groove 303 is located at the below of microchannel 108, thereby form the independent space isolated with microchannel 108, described negative pressure generation module top 302 is provided with a gas flow opening 304, described gas circuit opening 304 is connected with negative pressure groove 303 by the 2nd PE pipe 305 suitable with it, surround into a rectangular platform 308 in the middle of described negative pressure groove 303, with described elastica 2, be close to and corresponding to its top described microchannel 108, described rectangular platform 308 length are 1.5 * 10
4μ m, wide is 1.0 * 10
3μ m, described rectangular platform 308 and elastica 2 be bonding not, adds liquid lubricant, makes it can move each other under suction function, described negative pressure groove 303 1 sides also are located at the negative pressure Buffer Pool 306 connected with it, described the 2nd PE pipe 305 is connected with negative pressure groove 303 by negative pressure Buffer Pool 306, described negative pressure Buffer Pool 306 connects with negative pressure groove 303 by a groove 307, described the 2nd PE pipe 305 is vertically connected at negative pressure Buffer Pool 306 bottoms, the top 302 of described negative pressure generation module is rectangle, and this rectangular length is 2.5-3.0 * 10
4μ m, wide is 2.0-2.5 * 10
4μ m, described negative pressure groove 303 is the 3rd rectangular structure, and its cross section is rectangle, and height is 5.0 * 10
2μ m, wide is 2.5 * 10
2μ m, described negative pressure Buffer Pool 306 is the cylindrical cavity shape perpendicular to bottom 301, and the diameter of described cylindrical cavity is 5.0 * 10
3μ m, height is 1.0 * 10
3μ m, described groove 307 is the 4th rectangular structure, and its length is 3.0 * 10
3μ m, wide is 5.0 * 10
2μ m, height is 5.0 * 10
2μ m, described gas circuit opening 304 is circular port gas circuit opening, and the diameter of described circular port gas circuit opening 304 is 8.0 * 10
2μ m.
As shown in Figure 2, arteries of the present invention is simulated micro-fluidic system, comprise arteries simulation micro fluidic device 4 described above, also comprise cell cultures drive system 5 and negative pressure generator 6, described cell cultures drive system 5 is connected with microchannel 108 with fluid outlet 106 by fluid intake 105, the liquid-flow that described cell cultures drive system 5 drives in microchannel 108; Described negative pressure generator 6 is connected to gas flow opening 304 by the 2nd PE pipe 305 and is connected with negative pressure generation module, for making negative pressure generation module, produces negative pressure.
During use, at first the fluid intake 105 by microchannel module 1 adds microchannel 108 by cell suspension, at 37 ℃, under 5% carbon dioxide conditions, make cell attachment on the elastica 2 of microchannel 108 bottoms, then, the fluid intake of microchannel 108 105 is connected with cell culture medium drive system 5 with fluid outlet 106, again the gas circuit opening of negative pressure generation module 3 304 is connected with negative pressure generator 6 by the 2nd PE pipe, then, start cell culture medium drive system 5, cell culture medium drive system 5 can drive the liquid-flow in microchannel 108, thereby the cell adhered in the interior substrate of microchannel 108 is produced to hydrodynamic shear, and in the negative pressure groove 303 that the negative pressure that negative pressure generator 6 produces can be conducted in negative pressure generation module 3 by the 2nd PE pipe 305, make the elastica 2 of negative pressure groove 303 tops that deformation occur, thereby pull the elastica 2 that is affixed on rectangular platform, make it the deformation of occurred level direction, thereby make to attach superincumbent cell and be subject to mechanical stretching force.Because elastica 2 is very little in the deformation be parallel on the passage long axis direction, can ignore, if what be applied to cell on elastica 2 and elastica advocates perpendicular to the passage long axis direction, therefore, the stressing conditions of cell is: be parallel to the hydrodynamic shear of channel direction and perpendicular to the mechanical stretching force of channel direction.
concrete test example
test example 1
Elastica (PDMS film) (being printed on fluorescently-labeled protein arrays above it) is positioned over to arteries simulation micro fluidic device of the present invention to be stretched, result as shown in Figure 3, through negative pressure stretching Descemets membrane, with the elastica before stretching, compare, extensibility reaches 25%, its extensibility and homogeneity can produce a desired effect, and can meet the needs of simulation in vivo test fully.
test example 2
By MSC cell (Bone Marrow Stromal Stem Cells, take from SD rat (purchased from Beijing dimension tonneau China laboratory animal company), extracting method is with reference to carrying out with Publication about Document: Bosnakovski D, Mizuno M, Kim G, Takagi S, Okumura M, Fujinaga T.Isolation and multilineage differentiation of bovine bone marrow mesenchymal stem cells.Cell Tissue Res2005; 319:243-53.) input arteries of the present invention simulation micro fluidic device, stretch separately and compare with the result of shearing separately with the MSC cell, as shown in Figure 4, stretching can make the skeleton of cell arrange along the drawing force parallel direction separately as can be seen from this figure, and hydrodynamic shear can make cytoskeleton arrange along the shearing force direction separately; Drawing force and hydrodynamic shear can make the arrangement of cytoskeleton present the trend identical with resultant direction with joint efforts.Therefore, hydrodynamic shear and the drawing force material impact that is arranged with to the blood vessel inner cell, thus the powerful that arteries simulation micro fluidic device of the present invention is correlative study is described.
Claims (12)
1. an arteries is simulated micro fluidic device, this device comprises transparent microchannel module and the transparent negative pressure generation module suitable with it, described microchannel module bottom is connected by elastica with negative pressure generation module top, described microchannel module flows for fluid, and described negative pressure generation module is for generation of the negative pressure that makes elastica generation deformation;
Described microchannel module top is provided with fluid outlet and fluid intake, and described fluid outlet and fluid intake be respectively by with fluid intake and the suitable PE pipe of fluid outlet, being connected in the microchannel of microchannel module bottom, and connects with it;
Described negative pressure generation module top is provided with the negative pressure groove, and described negative pressure groove is located at the microchannel below, and described negative pressure generation module top is provided with a gas circuit opening, and described gas circuit opening is connected with the negative pressure groove by the 2nd PE pipe suitable with it.
2. arteries simulation micro fluidic device according to claim 1, is characterized in that, described negative pressure groove one side also is provided with the negative pressure Buffer Pool connected with it, and described the 2nd PE pipe is connected with the negative pressure groove by the negative pressure Buffer Pool.
3. arteries simulation micro fluidic device according to claim 2, is characterized in that, described negative pressure Buffer Pool connects by a groove and negative pressure groove, and preferably, described the 2nd PE pipe is vertically connected at negative pressure Buffer Pool bottom.
4. according to the described arteries simulation of any one in claims 1 to 3 micro fluidic device, it is characterized in that, surround into a rectangular platform in the middle of described negative pressure groove, with described elastica, be close to and corresponding to its top described microchannel, be filled with liquid lubricant between described rectangular platform and elastica, preferably, the bottom of described negative pressure generation module and top involution are and into a single integrated structure, and described rectangular platform length is 1.5 * 10
4μ m, wide is 1.0 * 10
3μ m.
5. according to the described arteries simulation of any one in claim 1 to 4 micro fluidic device, it is characterized in that, described microchannel is the second rectangular structure, it consists of the 3rd, the 4th sidewall and microchannel bottom, described microchannel bottom consists of elastica, preferably, the length of described the second rectangular parallelepiped is 1.8 * 10
4μ m, wide is 1.5 * 10
3μ m, height is 0.5 * 10
3μ m.
6. according to the described arteries simulation of any one in claim 1 to 5 micro fluidic device, it is characterized in that, the top of described microchannel module and bottom connect into by first, second sidewall the first rectangular structure that horizontal direction connects, preferably, the length of described the first rectangular parallelepiped is 2.5-3.0 * 10
4μ m, wide 2.0-2.5 * 10
4μ m, height is 3.0-5.0 * 10
3μ m.
7. according to the described arteries simulation of any one in claim 1 to 6 micro fluidic device, it is characterized in that, described microchannel module, negative pressure generation module and elastica are made by the polydimethylsiloxane material.
8. according to the described arteries simulation of any one in claim 1 to 7 micro fluidic device, it is characterized in that, described fluid outlet and fluid intake are circular port, and preferably, the diameter of described circular port is 8.0 * 10
2μ m; A described PE pipe is vertically connected at described microchannel module bottom.
9. according to the described arteries simulation of any one in claim 1 to 8 micro fluidic device, it is characterized in that, the top of described negative pressure generation module is rectangle, and this rectangular length is 2.5-3.0 * 10
4μ m, wide is 2.0-2.5 * 10
4μ m, described negative pressure groove is the 3rd rectangular structure, and its cross section is rectangle, and height is 5.0 * 10
2μ m, wide is 2.5 * 10
2μ m; Described negative pressure Buffer Pool is the cylindrical cavity shape perpendicular to platform area, and the diameter of described cylindrical cavity is 5.0 * 10
3μ m, height is 1.0 * 10
3μ m; Described groove is the 4th rectangular structure, and its length is 3.0 * 10
3μ m, wide is 5.0 * 10
2μ m, height is 5.0 * 10
2μ m; Described gas circuit opening is circular port, and preferably, the diameter of described circular port is 8.0 * 10
2μ m.
10. according to the described arteries simulation of any one in claim 1 to 9 micro fluidic device, it is characterized in that, described microchannel film piece and negative pressure produce the film block length and are 2.5-3.0 * 10
4μ m, wide 2.0-2.5 * 10 that are
4μ m, thick 3.0-5.0 * 10 that are
3μ m; Described elastica for long 2.5-3.0 * 10
4μ m, wide 2.0-2.5 * 10
4μ m, thick is 10-100 μ m.
11. simulate micro fluidic device in arteries physiological and pathological Mechanism Study, drug screening or the application in the test kit for the preparation of biological detection according to the described arteries of any one in claim 1 to 10, preferably, the test kit that described test kit is arteries physiological and pathological Mechanism Study or drug screening.
12. the test kit for biological detection, it is characterized in that, described test kit comprises the described arteries simulation of any one micro fluidic device in claim 1 to 10, also comprise detection reagent and damping fluid, preferably, described detection reagent is vasoactive small molecules, cytokine, antibody or the medicine for screening.
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| CN109012768B (en) * | 2017-06-09 | 2021-11-19 | 国家纳米科学中心 | Microfluidic liquid one-way flow control structure, chip and method |
| CN107134208A (en) * | 2017-07-14 | 2017-09-05 | 安疗生命科学（武汉）有限公司 | A kind of external intervention embolization simulation system |
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