CN103146573B - 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 biomedicine technical field.
Background technology
Abnormal blood flow kinetic factor is one of critical risk factor causing cardiovascular and cerebrovascular diseases, but its mechanism of action it be unclear that, and the limitation of traditional research method hinders Developments.In recent years, the foundation of the outer research model of vascular bodies and application facilitate the progress of correlative study greatly.The haemodynamics in vitro study model of blood vessel produces mechanical stimulation kind when can flow through blood vessel according to they simulate blood is divided three classes, i.e. hydrodynamic shear model, Tensile stress model, hydrodynamic shear and Tensile stress interaction model.Hydrodynamic shear model mainly adopts laminar flow plate, and liquid applies fluid shear stress by the liquid-inlet and outlet being opened on both sides to the cell being planted in substrate; Tensile stress model then applies mechanical stretching stimulation by the deformation of elastica or plate to the superincumbent cell of adhesion.First two model can inquire into the Behavioral change of cell in single mechanical stimulation situation, but, be a complex environment having multiple mechanical stimulation in organism residing for cell, a cardiovascular systems in vitro study model closer to internal milieu must consider the effect of multiple mechanical stimulation to cell.In recent years, people design and improve the device (Moore that some can apply hydrodynamic shear and Tensile stress simultaneously, J.E., Burki, E., Suciu, A., Zhao, S.M., Burnier, M., Brunner, H.R.and Meister, J.J. (1994) A Device for Subjecting Vascular Endothelial-Cells toBoth Fluid Shear-Stress and Circumferential Cyclic Stretch.Ann Biomed Eng.22,416-422, Qiu, Y.C.and Tarbell, J.M. (2000) Interaction between wallshear stress and circumferential strain affects endothelial cell biochemicalproduction.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 ofshear stress and cyclic stretch.J Biotechnol.133, 239-244), its the most basic principle is exactly the silicone rubber tube simulated blood vessel having attached endotheliocyte with inwall, keep applying Tensile stress by the expansion of tube chamber to the cell adhered to when certain pressure in tube chamber, apply shear-stress by washing away of liquid to cell simultaneously.But, the shortcoming of said apparatus also clearly, namely cell in the bad control of the adhesion of tube wall, Real Time Observation and intervention etc. can not be carried out to the behavior of cell under mechanical stimulation, these problems also govern the progress of correlative study.In recent years, the fast development of microflow control technique is that the foundation of numerous disease pathological study model provides opportunity, micro-fluidic chip can provide closer to the microenvironment under physiology, pathological conditions for cell, can mating surface chemistry and Soft lithograph technology cell behavior is manipulated and intervenes, observation and analysis can also be carried out at cell colony and unicellular two kinds of levels to the Behavioral change of cell.(the Huh such as Huh, D., Matthews, B.D., Mammoto, A., Montoya-Zavala, M., Hsin, H.Y.and Ingber, D.E. (2010) ReconstitutingOrgan-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, its manufacture craft is relatively complicated, because film does not have upholder, easy distortion, not easily 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 offluid and solid mechanical stresses contribute to cell death and detachment in amicrofluidic 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, liquid-gas interface can be formed, the microenvironment of simulated lung cystencyte.But above-mentioned micro fluidic device is only suitable for making alveolar model, and 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 object of the invention is to have for the external model of existing simulation arteries physio-pathological condition can not provide hydrodynamic shear and mechanical stretching force two kinds stimulation 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, the external model of some physiology, pathomechanism research can be built, 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 is used for fluid flowing, and described negative pressure generation module is for generation of the negative pressure making elastica generation deformation;
Described microchannel module top is provided with fluid intake and fluid outlet, and described fluid intake and fluid outlet are connected to the microchannel of microchannel module bottom respectively by with fluid intake and the suitable PE pipe of fluid outlet, and connect with it;
Described negative pressure generation module top is provided with negative pressure groove, described negative pressure groove is located at the below of microchannel, thus 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 by being connected with negative pressure groove with its 2nd suitable PE pipe.
Preferably, described negative pressure groove side is also provided with the negative pressure Buffer Pool connected with it, and described 2nd PE pipe is connected with negative pressure groove by negative pressure Buffer Pool.
Preferably, described negative pressure Buffer Pool is connected by a groove and negative pressure groove, and preferably, described 2nd PE pipe is vertically connected at bottom negative pressure Buffer Pool.
Preferably, a rectangular platform is surrounded in the middle of described negative pressure groove, being close to described elastica and corresponding to the described microchannel above it, between described rectangular platform and elastica, being filled with liquid lubricant, issuing looks movement mutually for making in the effect of negative pressure.
Preferably, described rectangular platform length is 1.5 × 10
4μm, wide is 1.0 × 10
3μm described negative pressure generation module top and bottom involution are structure as a whole.
Preferably, described microchannel is the second rectangular structure, and it is by bottom the 3rd, the 4th sidewall and microchannel and form bottom microchannel, and be made up of elastica bottom described microchannel, preferably, the length of described second rectangular parallelepiped is 1.8 × 10
4μm, wide is 1.5 × 10
3μm, height is 0.5 × 10
3μm.
Preferably, the top of described microchannel module and bottom connect into the first through rectangular structure of horizontal direction by first, second sidewall, and preferably, the length of described first rectangular parallelepiped is 2.5-3.0 × 10
4μm, wide 2.0-2.5 × 10
3μm, height is 3.0-5.0 × 10
3μm.
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
2μm; 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
4μm, wide is 2.0-2.5 × 10
4μm, described negative pressure groove is the 3rd rectangular structure, and its cross section is rectangle, and height is 5 × 10
2μm, wide is 2.5 × 10
2μm; Described negative pressure Buffer Pool is in the cylindrical cavity shape perpendicular to platform area, and the diameter of described cylindrical cavity is 5.0 × 10
3μm, height is 1.0 × 10
3μm; Described groove is the 4th rectangular structure, and its length is 3.0 × 10
3μm, wide is 5 × 10
2μm, height is 5 × 10
2μm; 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
2μm.
Preferably, described microchannel module and negative pressure generation module length are 2.5-3.0 × 10
4μm, be widely 2.0-2.5 × 10
4μm, be thickly 3.0-5.0 × 10
3μm; Described elastica is long 2.5-3.0 × 10
4μm, wide 2.0-2.5 × 10
4μm, thick is 10-100 μm.
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 a kind of arteries simulation micro fluidic device for the preparation of the application in the test kit of biological detection, preferably, described test kit is the test kit of 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, by the micro fluidic device of 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, and structure is simple, is easy to make and use; Optically transparent material makes, be easy to the situation in naked eyes or Microscopic observation passage, can change arbitrarily between microscope and incubator, can realize the original position dynamic monitoring of cell under two kinds of mechanical stimulations and under chemical stimulation, size, the frequency of two kinds of mechanical stimulations are adjustable at any time, can change the chemical micro-environment of cell at any time.
Accompanying drawing explanation
Below, describe embodiment of the present invention in detail by reference to the accompanying drawings, wherein:
Fig. 1 is the structural representation of arteries of the present invention simulation micro fluidic device;
Fig. 2 is the structural representation of arteries of the present invention simulation microfluidic system;
Fig. 3 is that described elastica is positioned over arteries of the present invention simulation micro fluidic device (only having negative pressure generation module) and carries out the experimental result schematic diagram that stretches, 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 MSC cell after Bone Marrow Stromal Stem Cells (MSC) being inputted arteries of the present invention simulation micro fluidic device and shears separately the experimental result schematic diagram carrying out contrasting, in figure, a is the experimental result schematic diagram that MSC cell stretches separately, b is the experimental result schematic diagram that MSC cell is sheared separately, and c is MSC cell drawn and the experimental result schematic diagram after shearing in the apparatus of the present;
Wherein:
1 is microchannel module, 101 is the top of microchannel module, 102 is the bottom of 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 be microchannel, 1081 is microchannel top, 1082 is bottom microchannel, 1083 be the 3rd sidewall, 1084 is the 4th sidewall;
2 is elastica;
3 is negative pressure generation module, and 301 is the bottom of negative pressure generation module, and 302 is the top of negative pressure generation module, 303 is negative pressure groove, and 304 is gas flow opening, 303 negative pressure grooves, 305 be the 2nd PE pipe, 306 negative pressure cushion chambers, 307 be groove, 308 be rectangular platform;
4 is arteries simulation micro fluidic device; 5 is 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, elastica 2 is passed through through plasma oxidation process covalent bonding in described microchannel module bottom and negative pressure generation module top, 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
4μm, wide 2.0-2.5 × 10
4μm, thick is the springform 2 of 10-100 μm, and described microchannel module 1 is for liquid-flow, and described negative pressure generation module 3 is for generation of the negative pressure making elastica 2 that deformation occur, described microchannel module top 101 and bottom 102 connect into the first through rectangular structure of horizontal direction by first, second sidewall 103,104, and the length of described first rectangular parallelepiped is 2.5-3.0 × 10
4μm, wide 2.0-2.5 × 10
4μm, height is 3.0-5.0 × 10
3μm, described microchannel module is long is 2.5-3.0 × 10
4μm, wide is 2.0-2.5 × 10
4μm, thick is 3.0-5.0 × 10
3μm, described microchannel module top 101 is provided with fluid intake 105 and fluid outlet 106, described fluid intake 105 and fluid outlet 106 are vertically connected at the microchannel 108 of microchannel module bottom 102 respectively by with fluid intake 105 and the suitable PE pipe 107 of fluid outlet 106, described microchannel 108 is in the second rectangular structure, it is by microchannel top, bottom 1081, 1082 and the 3rd, 4th sidewall 1083, 1084 are formed, and connect with it, be made up of elastica bottom described microchannel, the length of described second rectangular parallelepiped is 1.8 × 10
4μm, wide is 1.5 × 10
3μm, height is 5.0 × 10
2μm, described fluid intake 105 and fluid outlet 106 are circular port, and the diameter of described circular port is 8.0 × 10
2μm, the bottom 301 of described negative pressure generation module 3 and top 302 involution and into a single integrated structure, it is long 2.5-3.0 × 10 that described negative pressure produces film block
4μm, wide 2.0-2.5 × 10
4μm, thick is 3.0-5.0 × 10
3μm PDMS module, 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, thus 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 by being connected with negative pressure groove 303 with its 2nd suitable PE pipe 305, a rectangular platform 308 is surrounded in the middle of described negative pressure groove 303, be close to described elastica 2 and correspond to the described microchannel 108 above it, described rectangular platform 308 length is 1.5 × 10
4μm, wide is 1.0 × 10
3μm, described rectangular platform 308 and elastica 2 not bonding, adding liquid lubricant, makes it can move each other under suction function, the negative pressure Buffer Pool 306 connected with it is also located in described negative pressure groove 303 side, described 2nd PE pipe 305 is connected with negative pressure groove 303 by negative pressure Buffer Pool 306, described negative pressure Buffer Pool 306 is connected with negative pressure groove 303 by a groove 307, described 2nd PE pipe 305 is vertically connected at bottom negative pressure Buffer Pool 306, the top 302 of described negative pressure generation module is rectangle, and this rectangular length is 2.5-3.0 × 10
4μm, wide is 2.0-2.5 × 10
4μm, described negative pressure groove 303 is in the 3rd rectangular structure, and its cross section is rectangle, and height is 5.0 × 10
2μm, wide is 2.5 × 10
2μm, described negative pressure Buffer Pool 306 is in the cylindrical cavity shape perpendicular to bottom 301, and the diameter of described cylindrical cavity is 5.0 × 10
3μm, height is 1.0 × 10
3μm, described groove 307 is in the 4th rectangular structure, and its length is 3.0 × 10
3μm, wide is 5.0 × 10
2μm, height is 5.0 × 10
2μm, 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
2μm.
As shown in Figure 2, arteries of the present invention simulates 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, and described cell cultures drive system 5 drives the liquid-flow in microchannel 108; Described negative pressure generator 6 is connected to gas flow opening 304 and negative pressure generation model calling by the 2nd PE pipe 305, produces negative pressure for making negative pressure generation module.
During use, first by the fluid intake 105 of microchannel module 1, cell suspension is added microchannel 108, at 37 DEG C, under 5% carbon dioxide conditions, make in the elastica 2 of cell attachment bottom microchannel 108, then, the fluid intake 105 of microchannel 108 is connected with cell culture medium drive system 5 with fluid outlet 106, again the gas circuit opening 304 of negative pressure generation module 3 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, thus hydrodynamic shear is produced to the cell that substrate in microchannel 108 is adhered to, and the negative pressure that negative pressure generator 6 produces can be conducted in the negative pressure groove 303 in negative pressure generation module 3 by the 2nd PE pipe 305, make the elastica 2 above negative pressure groove 303 that deformation occur, thus pull the elastica 2 being affixed on rectangular platform, make it the deformation in occurred level direction, thus make the superincumbent cell of attaching be subject to mechanical stretching force.Because elastica 2 is to be parallel to the deformation on passage long axis direction very little, negligible, if what be applied to cell in elastica 2 and elastica advocates perpendicular to passage long axis direction, therefore, the stressing conditions of cell is: be parallel to the hydrodynamic shear of channel direction and the mechanical stretching force perpendicular to channel direction.
concrete test example
test example 1
Elastica (PDMS film) (being printed on fluorescently-labeled protein arrays above it) is positioned over arteries of the present invention simulation micro fluidic device to stretch, result as shown in Figure 3, through negative pressure stretching Descemet's membrane, compared with the elastica before stretching, extensibility reaches 25%, its extensibility and homogeneity can produce a desired effect, and can meet the needs of simulation in vivo test completely.
test example 2
By MSC cell (Bone Marrow Stromal Stem Cells, take from SD rat (purchased from Beijing laboratory animal company of dimension tonneau China), 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 multilineagedifferentiation 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 with MSC cell and to compare with the result sheared separately, as shown in Figure 4, stretch separately as can be seen from this figure and the skeleton of cell can be made along the arrangement of drawing force parallel direction, and hydrodynamic shear can make cytoskeleton arrange along shearing force direction separately; Drawing force then can make the arrangement of cytoskeleton present the trend identical with resultant direction with hydrodynamic shear with joint efforts.Therefore, hydrodynamic shear and drawing force are arranged with material impact to intravascular cells, thus illustrate that arteries of the present invention simulation micro fluidic device is the powerful of correlative study.
Claims (18)
1. an 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 is used for fluid flowing, and described negative pressure generation module is for generation of the negative pressure making elastica generation deformation;
Described microchannel module top is provided with fluid outlet and fluid intake, and described fluid outlet and fluid intake are connected to the microchannel of microchannel module bottom respectively by with fluid intake and the suitable PE pipe of fluid outlet, and connect with it;
Described negative pressure generation module top is provided with negative pressure groove, and described negative pressure groove is located at below microchannel, and described negative pressure generation module top is provided with a gas circuit opening, and described gas circuit opening is by being connected with negative pressure groove with its 2nd suitable PE pipe;
Wherein, surround into a rectangular platform in the middle of described negative pressure groove, be close to described elastica and correspond to the described microchannel above it, between described rectangular platform and elastica, being filled with liquid lubricant;
Described microchannel is the second rectangular structure, and it is formed by bottom the 3rd, the 4th sidewall and microchannel, is made up of bottom described microchannel elastica.
2. arteries simulation micro fluidic device according to claim 1, it is characterized in that, described negative pressure groove side is also provided with the negative pressure Buffer Pool connected with it, and described 2nd PE pipe is connected with negative pressure groove by negative pressure Buffer Pool.
3. arteries simulation micro fluidic device according to claim 2, it is characterized in that, described negative pressure Buffer Pool is connected by a groove and negative pressure groove.
4. arteries simulation micro fluidic device according to claim 3, it is characterized in that, described 2nd PE pipe is vertically connected at bottom negative pressure Buffer Pool.
5. arteries according to any one of claim 1 to 4 simulation micro fluidic device, is characterized in that, the bottom of described negative pressure generation module and top involution and into a single integrated structure, and described rectangular platform length is 1.5 × 10
4μm, wide is 1.0 × 10
3μm.
6. arteries simulation micro fluidic device according to any one of claim 1 to 4, it is characterized in that, the length of described second rectangular parallelepiped is 1.8 × 10
4μm, wide is 1.5 × 10
3μm, height is 0.5 × 10
3μm.
7. arteries simulation micro fluidic device according to any one of claim 1 to 4, it is characterized in that, the top of described microchannel module and bottom connect into the first through rectangular structure of horizontal direction by first, second sidewall.
8. arteries simulation micro fluidic device according to claim 7, it is characterized in that, the length of described first rectangular parallelepiped is 2.5-3.0 × 10
4μm, wide 2.0-2.5 × 10
4μm, height is 3.0-5.0 × 10
3μm.
9. arteries simulation micro fluidic device according to any one of claim 1 to 4, it is characterized in that, described microchannel module, negative pressure generation module and elastica are made by polydimethyl siloxane material.
10. arteries simulation micro fluidic device according to any one of claim 1 to 4, it is characterized in that, described fluid outlet and fluid intake are circular port.
11. arteries simulation micro fluidic devices according to claim 10, it is characterized in that, the diameter of described circular port is 8.0 × 10
2μm; A described PE pipe is vertically connected at described microchannel module bottom.
12. arteries simulation micro fluidic devices according to any one of claim 1 to 4, 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
4μm, wide is 2.0-2.5 × 10
4μm, described negative pressure groove is the 3rd rectangular structure, and its cross section is rectangle, and height is 5.0 × 10
2μm, wide is 2.5 × 10
2μm; Described negative pressure Buffer Pool is in the cylindrical cavity shape perpendicular to platform area, and the diameter of described cylindrical cavity is 5.0 × 10
3μm, height is 1.0 × 10
3μm; Described groove is the 4th rectangular structure, and its length is 3.0 × 10
3μm, wide is 5.0 × 10
2μm, height is 5.0 × 10
2μm; Described gas circuit opening is circular port.
13. arteries simulation micro fluidic devices according to claim 12, it is characterized in that, the diameter of described circular port is 8.0 × 10
2μm.
14. arteries simulation micro fluidic devices according to any one of claim 1 to 4, it is characterized in that, described microchannel film block and negative pressure produce film block length and are 2.5-3.0 × 10
4μm, be widely 2.0-2.5 × 10
4μm, be thickly 3.0-5.0 × 10
3μm; Described elastica be long 2.5-3.0 × 10
4μm, wide 2.0-2.5 × 10
4μm, thick is 10-100 μm.
15. arteries simulation micro fluidic devices according to any one of claim 1 to 14 are in the arteries physiological and pathological Mechanism Study of non-diagnostic object, drug screening or for the preparation of the application in the test kit of biological detection.
16. application according to claim 15, is characterized in that, described test kit is the test kit of arteries physiological and pathological Mechanism Study or drug screening.
17. 1 kinds, for the test kit of biological detection, is characterized in that, described test kit comprises the arteries simulation micro fluidic device according to any one of claim 1 to 14, also comprises detection reagent and damping fluid.
18. test kits as claimed in claim 17, is characterized in that, described detection reagent is vasoactive small molecules, cytokine, antibody or the medicine for screening.
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| WO2016036536A1 (en) * | 2014-09-02 | 2016-03-10 | Bio-Rad Laboratories, Inc. | Microscale fluidic devices and components having a fluid retention groove |
| 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 |
| CN107134208B (en) * | 2017-07-14 | 2023-06-06 | 安疗生命科学（武汉）有限公司 | In-vitro interventional embolism treatment simulation system |
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| CN101603005A (en) * | 2008-06-13 | 2009-12-16 | 国家纳米科学中心 | A kind of pair cell applies the cell culture apparatus of mechanical stimulation |
| CN102140422A (en) * | 2010-02-02 | 2011-08-03 | 国家纳米科学中心 | Device for controlling interaction of various cells as well as preparation method and application thereof |
| CN102262162A (en) * | 2010-05-26 | 2011-11-30 | 中国科学院大连化学物理研究所 | Microfluidic chip system for studying mechanical behaviors of cells |
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| CN101603005A (en) * | 2008-06-13 | 2009-12-16 | 国家纳米科学中心 | A kind of pair cell applies the cell culture apparatus of mechanical stimulation |
| CN102140422A (en) * | 2010-02-02 | 2011-08-03 | 国家纳米科学中心 | Device for controlling interaction of various cells as well as preparation method and application thereof |
| CN102262162A (en) * | 2010-05-26 | 2011-11-30 | 中国科学院大连化学物理研究所 | Microfluidic chip system for studying mechanical behaviors of cells |
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