CN110295111A - A kind of device of bionical blood vessel network tumor-cell extravasation migration - Google Patents
A kind of device of bionical blood vessel network tumor-cell extravasation migration Download PDFInfo
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- CN110295111A CN110295111A CN201910637344.6A CN201910637344A CN110295111A CN 110295111 A CN110295111 A CN 110295111A CN 201910637344 A CN201910637344 A CN 201910637344A CN 110295111 A CN110295111 A CN 110295111A
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Abstract
A kind of device of bionical blood vessel network tumor-cell extravasation migration, including supporting layer, fluid flow layer, the pumping layer, gas-powered layer being from bottom to top sequentially overlapped, fluid flow layer is equipped with the first sprue, capilary chamber, the second sprue and the liquid chamber for being connected in series to form circulation of fluid circuit, check valve is respectively equipped in capilary chamber, the first sprue and the second sprue, gas-powered layer applies external periodic force to liquid chamber by pumping layer, to drive fluid one-way flow in fluid circuit, blood circulation of human body is simulated；Capilary chamber is separated with the first sprue and the second sprue by anti-spilled micro-pillar array, capilary chamber is provided with the inlet for injecting normal tissue cell mixed liquor, and the inlet for injecting culture solution and tumor cell suspension is provided on the first sprue and/or the second sprue.The present apparatus can be used for carrying out screening anticancer medicine, observation and quantify the transfer ability of cancer cell in the tissue.
Description
Technical field
The present invention relates to a kind of devices of bionical blood vessel network tumor-cell extravasation migration.
Background technique
About 90% cancer related mortality is as metastatic disease rather than caused by primary tumor.Cancer metastasis is primary
Property tumour in epithelial cell complete the cell biological events of a series of complex after formed, this sequence of events is referred to as
" invasion-transfer cascade " comprising primary tumor epithelial cell: pass through extracellular matrix and the stromal cells layers part of surrounding
Invasion are penetrated into Endovascular (interior infiltration), are survived in blood circulation as circulating tumor cell, after organ site at a distance
It stops, penetrates into distant organs (extravasation) across blood vessel, initially survival forms micrometastasis in heterogeneous microenvironment, is then turning
It moves position and restarts its propagation procedure, to generate macroscopic view, the detectable tumour growth of clinic.The process ratio of cancer metastasis
It is more complex, fail the drug for finding out complete inhibition transfer so far.And it is related to passing twice through blood vessel during cancer metastasis
Process, be respectively it is interior blend extravasation, and circulating tumor cell plays the role of " forming a connecting link " during cancer metastasis.Institute
To construct the self-organizing blood vessel network with human body physiological state and establish the blood flow model of class heart driving, Jin Eryan
Study carefully tumour cell dynamic extravasation process and carry out the screening of anticancer drug, is of great significance to research cancer metastasis.
Summary of the invention
It is a primary object of the present invention to overcome the deficiencies of the prior art and provide outside a kind of bionical blood vessel network tumour cell
Seep the device of migration.
To achieve the above object, the invention adopts the following technical scheme:
A kind of device of bionical blood vessel network tumor-cell extravasation migration, including the supporting layer being from bottom to top sequentially overlapped
(1), fluid flow layer (2), pumping layer (3), gas-powered layer (4)；Wherein, the fluid flow layer (2), which is equipped with, is connected in series
The first sprue (5), capilary chamber (7), the second sprue (6) and the liquid chamber (8) in circulation of fluid circuit are formed, it is described
Check valve (9), the gas are respectively equipped in capilary chamber (7), first sprue (5) and second sprue (6)
Body drives layer (4) to apply external periodic force by pumping layer (3) the Xiang Suoshu liquid chamber (8), to drive fluid described
One-way flow in fluid circuit simulates blood circulation of human body；The capilary chamber (7) and first sprue (5) and institute
It states the second sprue (6) to separate by anti-spilled micro-pillar array, the capilary chamber (7) is provided with for injecting normal tissue
The inlet (10,11) of cell mixture, normal tissue cell mixed liquor are limited in described micro- by the anti-spilled micro-pillar array
In blood vessel chamber (7), gel and self-organizing generation microvessel network, first sprue (5) and/or second sprue
(6) inlet (13,14) for injecting culture solution and tumor cell suspension is provided on, tumour cell passes through described anti-spilled
The capilary opening in micro-pillar array gap enters in the capilary chamber (7), and participates in system circulation.
So-called normal tissue cell mixed liquor typically contains normal tissue cell (such as bone tissue is normally thin in the present invention
Born of the same parents, lung's normal cell), fibrinogen, fibrin ferment and Human umbilical vein endothelial cells (HUVECs) mixed liquor.
Further, first sprue (5) and second sprue (6) are connected with the capilary chamber (7)
Position be respectively formed with the widened exterior chamber of lateral dimension relative to sprue, the inlet (13,14) sets respectively
At the both ends for setting the exterior chamber.
Further, the pumping layer (3) is provided with upper chamber (15) above the liquid chamber (8), described
Liquid chamber (8) is connected to the upper chamber (15), and the gas-powered layer (4) is arranged in the top of the upper chamber (15)
Have inflating cells (18), is separated between the inflating cells (18) and the upper chamber (15) by film, filled by described
The air inlet (19) of gas chamber (18) periodically inflates the inflating cells (18), drives the film to the upper chambers
Room (15) applies external periodic force, to generate periodically variable pressure in the liquid chamber (8), to drive the stream
Fluid flowing in body circuit.
Further, the gas-powered layer (4) is provided with and the inlet of the fluid flow layer (2) (13,14) phase
Corresponding through hole (20-23), and the through hole of connection corresponding with inlet (10,11) of the fluid flow layer (2)
(24,25), pumping layer (3) are provided with through hole corresponding with the inlet of the fluid flow layer (2) (13,14)
And the through hole (17) of connection corresponding with inlet (10,11) of the fluid flow layer (2) (16),.
Further, the anti-spilled micro-pillar array in the capilary chamber (7) is isosceles trapezoid fillet microtrabeculae battle array
It arranges (12).
Further, the isosceles trapezoid fillet microtrabeculae is spaced between 60~90 μm, and microtrabeculae long hem width degree is 120-
160 μm, short side width is 30-70 μm, it is preferable that is spaced in 70-80 μm, the long hem width degree of microtrabeculae is 140 μm, and short side width is 50
μm。
Further, the check valve (9) is made by PP material thin discs and PDMS material mixing casting.
Further, the supporting layer (1) is glass material.
Further, the fluid flow layer (2), the pumping layer (3), the gas-powered layer (4) are PDMS material.
Further, the supporting layer (1), the fluid flow layer (2), the pumping layer (3), the gas-powered layer
(4) it is assembled integrally by the bonding technology based on plasma cleaning technology.
The invention has the following beneficial effects:
The present invention proposes a kind of device of bionical blood vessel network tumor-cell extravasation migration, and the device provides one kind to be based on
Micro-fluidic chip class heart driving blood vessel network self-circulation system in study tumor cell extravasation model, from bottom to top according to
Secondary to be superimposed with supporting layer, fluid flow layer, pumping layer, gas-powered layer, by setting chamber and runner, simulation blood of human body is followed
Ring and microvessel network generate flowing under external periodic force effect, and in capilary regional perfusion tumour cell, so as to
It realizes the study tumor cell extravasation process in the system with the flox condition for meeting person's physiological state, is that cancer metastasis is related
Research provides new means.Wherein capilary chamber can be inoculated with different tissues normal cell and Human umbilical vein endothelial cells
(HUVECs), fibrinogen, fibrin ferment mixed solution, such as bone tissue normal cell, lung's normal cell etc., gel Cheng Wei
Different cancer cells is perfused after blood vessel, by different combinations, observes transfer ability of the same cancer cell in different tissues
And transfer ability of the different tumour cells in homologue.And it is outer to study tumour cell dynamic under different shear stresses
It seeps.
Compared with prior art, the embodiment of the present invention has the advantage that
Functionally, the present apparatus more meets human body physiological state model, containing the microvessel network that self-organizing generates, and
It realizes the class heart pumping more met under Human physiology state flox condition and drives sanguimotor tumor-cell extravasation mould
Type has more physiologic meaning.It can be used for carrying out screening anticancer medicine, observation simultaneously and quantify same cancer cell in difference
The transfer ability of transfer ability and different cancer cells in homologue in tissue.The design knot of four layers of chip of the present apparatus
Structure is made simply, mass production to may be implemented.
Detailed description of the invention
Fig. 1 is the structural representation for the device that the bionical blood vessel network tumor-cell extravasation of an embodiment of the present invention migrates
Figure；
Fig. 2 a and Fig. 2 b are respectively the structural schematic diagram of PDMS fluid flow layer shown in FIG. 1 and the enlarged drawing of part A；
Fig. 3 is that PDMS shown in FIG. 1 pumps the structural schematic diagram after being flipped up below layer；
Fig. 4 is the structural schematic diagram after being flipped up below PDMS gas-powered layer shown in FIG. 1.
Specific embodiment
It elaborates below to embodiments of the present invention.It is emphasized that following the description is only exemplary,
The range and its application being not intended to be limiting of the invention.
Refering to fig. 1 to Fig. 4, in one embodiment, a kind of device of bionical blood vessel network tumor-cell extravasation migration is wrapped
Include the supporting layer 1 being from bottom to top sequentially overlapped, fluid flow layer 2, pumping layer 3, gas-powered layer 4；Wherein, the fluid flowing
Layer 2 is equipped with the first sprue 5, capilary chamber 7, the second sprue 6 and the fluid chamber for being connected in series to form circulation of fluid circuit
Room 8 is respectively equipped with check valve 9, the gas in the capilary chamber 7, first sprue 5 and second sprue 6
Body drives layer 4 to apply external periodic force to the liquid chamber 8 by the pumping layer 3, to drive fluid to return in the fluid
One-way flow in road simulates blood circulation of human body, wherein first sprue 5 and second sprue 6 are for simulating people
Artery and/or vein in body blood circulation, the capilary chamber 7 is used to simulate the microvessel network of human body, in periodicity
Flowing is generated under external force, to simulate blood of human body flowing；The capilary chamber 7 and first sprue 5 and institute
It states the second sprue 6 to separate by anti-spilled micro-pillar array, the capilary chamber 7 is provided with for injecting normal tissue cell
The inlet 10,11 of mixed liquor, normal tissue cell mixed liquor are limited in the capilary chamber by the anti-spilled micro-pillar array
In room 7, simultaneously self-organizing generates microvessel network to gel, is provided on first sprue 5 and/or second sprue 6
For successively injecting the inlet 13,14 of culture solution and tumor cell suspension, after gel, culture solution is injected to sprue, to micro-
After angiogenesis into, the culture solution in system is changed to fresh tumor cell suspension, tumour cell passes through the anti-spilled microtrabeculae
The capilary opening in array gap enters in the capilary chamber 7, and participates in system circulation.The present apparatus provides use
In the blood vessel network self-circulation system of the class heart driving of study tumor cell extravasation.
Wherein inlet 10,11 is preferably provided with multiple, mixed liquor only can be added from one of mouth, for example, from feed liquor
Mixed liquors are added in mouth 10, and inlet 11 can regard venthole at this time, and culture can also be stored in hole after gel success
Liquid achievees the purpose that abundant feed flow.
When using the present apparatus, the capilary chamber 7 can be inoculated with different tissues normal cell and people by inlet 10
Huve cell HUVECs, fibrinogen, fibrin ferment mixed solution, such as bone tissue normal cell, lung are normally thin
Born of the same parents etc., and culture solution is loaded onto sprue by inlet 13,14, inlet 13,14 is also used as subsequent perfusion tumor cell suspension
Inlet after Angiogenesis into the culture solution in system is changed to fresh tumor cell suspension, tumour cell can be micro-
The capilary opening in column array gap enters in capilary, and participates in system circulation.In the present apparatus, the first sprue
5 can be used for simulating the artery in blood circulation of human body, and the second sprue 6 can be used for simulating the vein in blood circulation of human body,
Under Fluid pressure effect, two check valves are selectively passively opened or closed, and are generated by first sprue 5-capilary chamber
7-the second the 8-the first sprue of 6-liquid chamber of sprue, 5 one-way flow.Using the present apparatus, can be perfused different normal
Different cancer cells can also be perfused at capilary in histocyte mixing lyogel, and studies tumour cell under different shear stresses
Dynamic exosmoses.By different combinations, transfer ability of the same cancer cell of observable in different tissues and different swollen
Transfer ability of the oncocyte in homologue.
The present apparatus operationally controls simply, and external periodic force can be applied using programmable flow programmable instrument, inoculation
Cell, preparation fibrinogen and blood coagulation enzyme mixation, load culture solution, perfusion tumour cell are simple and easy, tumour cell
Situation and the Angiogenesis situation of exosmosing can realize static and dynamic observation by microscope and living cells work station, and chip can be into
Row high-temperature sterilization is handled and can be placed directly in carbon dioxide incubator and cultivates, and then guarantees sterile cell growing environment.
The present apparatus provides the external model for meeting the study tumor cell extravasation of Human physiology state, is by giving
It unites different external periodic forces, liquid flow velocity in system can be changed, and then change shear stress, so as to study not cocurrent flow
Tumor-cell extravasation situation under the conditions of dynamic finds new breakthrough point for treatment of cancer.The present apparatus can also be used for anticancer drug
The drug of screening, especially anticancer transfer.The present apparatus can be also used for observing and quantifying same cancer cell in different tissues
In transfer ability in homologue of transfer ability and different cancer cells.
In a preferred embodiment, first sprue 5 and second sprue 6 and 7 phase of capilary chamber
Position even is respectively formed with the widened exterior chamber of lateral dimension relative to sprue, and the inlet 13,14 is set respectively
At the both ends for setting the exterior chamber.
In a preferred embodiment, the pumping layer 3 is provided with upper chamber 15, institute in the top of the liquid chamber 8
It states liquid chamber 8 and is connected to the upper chamber 15, the gas-powered layer 4 is provided with inflation in the top of the upper chamber 15
Chamber 18 is separated between the inflating cells 18 and the upper chamber 15 by film, by the inflating cells 18 into
Port 19 periodically inflates the inflating cells 18, and the film is driven to apply outside periodicity to the upper chamber 15
Power, to generate periodically variable pressure in the liquid chamber 8, so that the fluid in the fluid circuit be driven to flow.
In a preferred embodiment, the gas-powered layer 4 is provided with the inlet 13,14 with the fluid flow layer 2
Corresponding through hole 20-23, and with the inlet 10 of the fluid flow layer 2,11 corresponding connections through hole 24,
25, the pumping layer 3 be provided with the inlet 13 of the fluid flow layer 2,14 corresponding through holes 16, and with it is described
The inlet 10 of fluid flow layer 2,11 corresponding connections through hole 17.
In a preferred embodiment, the anti-spilled micro-pillar array in the capilary chamber 7 is isosceles trapezoid fillet
Micro-pillar array 12.
In a more preferred embodiment, the isosceles trapezoid fillet microtrabeculae is spaced between 60~90 μm, microtrabeculae long side
Width is 120-160 μm, and short side width is 30-70 μm, it is preferable that is spaced in 70-80 μm, the long hem width degree of microtrabeculae is 140 μm, short
Hem width degree is 50 μm.
In a preferred embodiment, the check valve 9 is made by PP material thin discs and PDMS material mixing casting.
Specifically, it the processing such as can punch, open woodruff key, cutting, encapsulation by PP material thin discs and PDMS material mixing casting, rear pass through
Technique is made.Its structure can make liquid one-way flowing.
In a preferred embodiment, the supporting layer 1 is glass material.
In a preferred embodiment, the fluid flow layer 2, the pumping layer 3, the gas-powered layer 4 are PDMS material
Material.
In a preferred embodiment, the supporting layer 1, the fluid flow layer 2, the pumping layer 3, the gas-powered
Layer 4 is assembled integrally by the bonding technology based on plasma cleaning technology.
The present apparatus can be placed directly in carbon dioxide incubator and be cultivated, to guarantee to stablize sterile cell growth ring
Border.
The present apparatus can be used for simulating under different flow velocity conditions, and the extravasation ability and the death rate of tumour cell more accord with
Close the physiological status of human cancer cell's transfer；The screening of anticancer medicine can be carried out under this device, and then filter out needle
Fight the drug of cancer metastasis, and then more accurately treating cancer；It can be used for observing and quantifying same cancer cell with high throughput
The transfer ability of transfer ability and different cancer cells in homologue in different tissues.
Combined with specific embodiments below to the detailed description of the invention.
As shown in Figure 1, the device of bionical blood vessel network tumor-cell extravasation migration includes four layers of chip structure, from bottom to top
It is followed successively by sheet glass supporting layer 1, PDMS fluid flow layer 2, PDMS pumping layer 3, PDMS gas-powered layer 4.
The opposite two sides of capilary chamber 7 connect sprue 5,6, and in addition inlet 10,11 is arranged in opposite two sides.Micro- blood
When 7 feed liquor of lumen room, mixed solution can be entered by inlet 10, and the sky of capilary chamber 7 is discharged from another inlet opening 11
Gas, so that capilary chamber 7 can be sufficiently perfused in mixed liquor.Under the action of isosceles trapezoid fillet micro-pillar array 12, mixed liquor
It is limited in capilary chamber, without entering sprue 5,6.After mixing lyogel, culture solution is successive from inlet 13,14
It is injected to sprue 6,5.After corresponding liquid is perfused in all mouths, it can be dripped on each mouth with outside air connection
Culture solution.The capilary chamber 7 is having a size of 3.8mm × 1.1mm × 0.25mm (length × width × height), the size of sprue 5,6
For 0.6mm × 0.25mm wide × height.Isosceles trapezoid fillet micro-pillar array 12 is set in capilary chamber 7, in microfluidic surface
Under power effect, by the barrier of capilary region hydrogel solution inside capilary chamber 7, without entering runner 5 and 6.Liquid
Chamber 8 connects upper chamber 15 for storing culture solution, by applying external periodic force on 15 top of chamber, thus in liquid
Periodically variable pressure is generated in fluid chamber 8 and upper chamber 15, so that liquid be driven to flow to sprue 5.The fluid chamber
Room 8 is having a size of 5.5mm × 4.5mm × 0.25mm (length × width × height).PDMS pump layer 3 with a thickness of 0.4mm, middle chamber 15
Size is consistent with 8 size of its underpart liquid chamber, is 5.5mm × 4.5mm × 0.25mm (length × width × height).PDMS gas-powered
19 diameter of air inlet of layer 4 is 2-3mm.It is periodically inflated in the air inlet 19 of PDMS gas-powered layer 4, due to inflating cells
18 is closed, therefore inflating cells 18 also generate periodically variable pressure；Under 18 periodic pressure of inflating cells, upper chamber 15
The PDMS film on upper layer periodically pushes, and upper chamber 15 is given liquid chamber 8 under external periodic force effect and periodically pressed
Power, so that periodically driving 5 check valve of sprue is opened, liquid flows to sprue 5.
The processing assembling of chip is realized by following steps:
Firstly, chip manufacturing.Sheet glass supporting layer 1 select common optical glass 51mm × 21mm × 1mm (it is long × wide ×
It is high), before chip assembling, it is necessary to be cleaned and be dried to sheet glass.Secondly, PDMS fluid flow layer 2, PDMS pumping layer 3,
The processing method that the mold of PDMS gas-powered layer 4 uses soft lithographic, is spin-coated on silicon wafer with SU-8 photoresist, preparatory in placement
Designed mask plate, and under litho machine be aligned exposure, obtain mold after development, after in mold upper PDMS liquid, Gu
It is taken off after change and obtains the chip with micro-structure.Finally process PDMS fluid flow layer 2, PDMS pumping layer 3, PDMS gas
The outer dimension of driving layer 4 be respectively 48mm × 18mm × 1mm (length × width × height), 48mm × 18mm × 0.4mm (it is long × wide ×
It is high), 48mm × 18mm × 1mm (length × width × height) wherein, check valve is symmetrically disposed at the flowing of PDMS fluid after being fabricated separately
On the sprue 5 and 6 of layer 2.
The pre-treatment of micro-fluidic chip operates: first micro-fluidic chip being placed in the ethyl alcohol that concentration is 75% and is tentatively disappeared
Poison；PBS phosphate buffer is used again, and pH value is 7.4 chambers and runner for being passed through chip, is cleaned 3 times, residual when removing alcohol disinfecting
Stay alcohol；Then micro-fluidic chip is put into high-pressure sterilizing pot and carries out sterilization processing；Micro-fluidic chip is put into 80 DEG C of baking ovens again
In carry out hydrophobic treatment for 24 hours.1h is irradiated finally, micro-fluidic chip is placed under ultraviolet light, again sterilization processing.
Secondly, Angiogenesis.As shown in Fig. 2 a to 2b, upper all constructional depths of PDMS fluid flow layer 2 are 250 μ
m.Firstly, can block inlet 24/25 one of those, in the Slow loading Human umbilical vein endothelial cells of another mouthful
HUVECs, fibrinogen, fibrin ferment mixed solution prevent from overflowing micro-pillar array 12.In humidity box after gel 15 minutes, by
Culture solution inlet 20 loads liquid, blocks other three holes 21,22,23, until liquid is loaded onto capilary chamber 7 and mainstream
The midline of chamber between road, after block 20,22,23, from inlet 21 load culture solution up to middle line liquid joint, and
Sprue 6 is continued to fill up, check valve is opened under fluid pressure effect, and liquid can fill liquid chamber 8, in liquid pressure masterpiece
With lower further opening check valve, fill sprue 5, and fill the cavity between capilary chamber and sprue 5, air by into
Liquid mouth 22,23 is discharged.After having loaded culture solution, places a device into incubator and realize that dynamic is real in culture or living cells work station
When observe capilary forming process.The every 24H of device changes liquid, Angiogenesis after 3-4 days, and picking out between microtrabeculae has 50% micro- blood
Tumour cell device is perfused in tube opening, and prepares that tumour cell is perfused.
Wherein final concentration of 12 × 10 Human umbilical vein endothelial cells HUVECs6A/ml, fibrin ferment 4U/ml, fibrin
It originally is 6mg/ml.Because fibrinogen is added after fibrin ferment in 30 seconds inner gels, therefore capilary should be added immediately after three's mixing
Chamber 7, and instant mixed solution, have residue that can not reuse, and fibrinogen and fibrin ferment should dispense, current existing
Match.
Finally, tumour cell is perfused and generates flowing.The concentration that tumour cell is perfused is 0.5 × 106A/ml, firstly, slow
Old culture solution in slow suction means, prepared tumor cell suspension is loaded onto from inlet 22,23 with same method
In the capilary of sprue 56, liquid chamber 8 and capilary chamber 7.Inlet 20,21,22,23,24,25 is blocked, by steel needle
Insertion air inlet 19 simultaneously ensures to be interference fitted, cavity seal.The external programmable flow programmable instrument of steel needle changes the week of gas pumping
Phase to increase the pressure of chamber 18, and then increases the pressure of chamber 8, and the check valve of sprue 5 is opened, and liquid realizes stream
Dynamic, flowing velocity is determined by the pressure of chamber.After starting flow programmable instrument, outside living cells work station dynamic observation tumour cell
Infiltration process, and choose suitable timing node and carry out quantization record, summarize influence of the different shear stresses to tumor-cell extravasation.
Wherein, haemodynamics shear stress, the physical force that the cell in blood is applied due to blood flow.It is single
Position: dyne/cm2.Calculation: shear stress is equal to fluid viscosity (μ) and shear rate d γ/dt (d γ/dt=8vav/ d)
Product, wherein vavFor mean blood flow velocity, d is blood vessel diameter, and blood viscosity μ is about 4cP (centipoise).
If studying transfer ability of the different tumour cells in homologue, the type of perfusion tumour cell is needed to change.If
Transfer ability of the same tumor cell in different tissues is studied, needs to add one kind when loading mixed liquor in capilary chamber
Normal tissue cell.If carrying out screening anticancer medicine, drug need to be only loaded into tumor cell suspension.
The above content is combine it is specific/further detailed description of the invention for preferred embodiment, cannot recognize
Fixed specific implementation of the invention is only limited to these instructions.For those of ordinary skill in the art to which the present invention belongs,
Without departing from the inventive concept of the premise, some replacements or modifications can also be made to the embodiment that these have been described,
And these substitutions or variant all shall be regarded as belonging to protection scope of the present invention.
Claims (10)
1. a kind of device of bionical blood vessel network tumor-cell extravasation migration, which is characterized in that including being from bottom to top sequentially overlapped
Supporting layer (1), fluid flow layer (2), pumping layer (3), gas-powered layer (4)；Wherein, the fluid flow layer (2) is equipped with
It is connected in series to form the first sprue (5), capilary chamber (7), the second sprue (6) and the liquid chamber in circulation of fluid circuit
(8), check valve is respectively equipped in the capilary chamber (7), first sprue (5) and second sprue (6)
(9), the gas-powered layer (4) applies external periodic force by pumping layer (3) the Xiang Suoshu liquid chamber (8), with driving
Fluid one-way flow in the fluid circuit simulates blood circulation of human body；The capilary chamber (7) and first mainstream
Road (5) and second sprue (6) are separated by anti-spilled micro-pillar array, and the capilary chamber (7) is provided with for infusing
Enter the inlet (10,11) of normal tissue cell mixed liquor, normal tissue cell mixed liquor is limited by the anti-spilled micro-pillar array
For system in the capilary chamber (7), gel and self-organizing generate microvessel network, first sprue (5) and/or described
The inlet (13,14) for injecting culture solution and tumor cell suspension is provided on second sprue (6), tumour cell passes through
The capilary opening in the anti-spilled micro-pillar array gap enters in the capilary chamber (7), and participates in system circulation
In.
2. the device of bionical blood vessel network tumor-cell extravasation migration as described in claim 1, which is characterized in that described first
The position that sprue (5) and second sprue (6) are connected with the capilary chamber (7) is respectively formed with relative to mainstream
The widened exterior chamber of the lateral dimension in road, the inlet (13,14) are respectively set at the both ends of the exterior chamber.
3. the device of bionical blood vessel network tumor-cell extravasation migration as claimed in claim 1 or 2, which is characterized in that described
Pumping layer (3) is provided with upper chamber (15) above the liquid chamber (8), and the liquid chamber (8) is connected on described
Portion's chamber (15), the gas-powered layer (4) is provided with inflating cells (18) above the upper chamber (15), described to fill
Separated between gas chamber (18) and the upper chamber (15) by film, passes through the air inlet (19) of the inflating cells (18)
The inflating cells (18) are periodically inflated, the film is driven to apply external periodic force to the upper chamber (15),
To generate periodically variable pressure in the liquid chamber (8), so that the fluid in the fluid circuit be driven to flow.
4. the device of bionical blood vessel network tumor-cell extravasation migration as described in any one of claims 1 to 3, feature exist
In the gas-powered layer (4) is provided with through hole corresponding with the inlet of the fluid flow layer (2) (13,14)
(20-23), and the through hole (24,25) of connection corresponding with inlet (10,11) of the fluid flow layer (2), it is described
Pumping layer (3) is provided with through hole (16) corresponding with the inlet of the fluid flow layer (2) (13,14), and with institute
State the through hole (17) of inlet (10,11) corresponding connection of fluid flow layer (2).
5. such as the device of the described in any item bionical blood vessel network tumor-cell extravasation migrations of Claims 1-4, feature exists
In the anti-spilled micro-pillar array in the capilary chamber (7) is isosceles trapezoid fillet micro-pillar array (12).
6. the device of bionical blood vessel network tumor-cell extravasation migration as claimed in claim 5, which is characterized in that the isosceles
The microtrabeculae of trapezoidal fillet microtrabeculae is spaced between 60~90 μm, and the long hem width degree of microtrabeculae is 120-160 μm, and short side width is 30-
70 μm, it is preferable that be spaced in 70-80 μm, the long hem width degree of microtrabeculae is 140 μm, and short side width is 50 μm.
7. such as the device of bionical blood vessel network tumor-cell extravasation migration as claimed in any one of claims 1 to 6, feature exists
In the check valve (9) is made by PP material thin discs and PDMS material mixing casting.
8. the device of bionical blood vessel network tumor-cell extravasation migration as described in any one of claim 1 to 7, feature exist
In the supporting layer (1) is glass material.
9. the device of bionical blood vessel network tumor-cell extravasation migration as claimed in any one of claims 1 to 8, feature exist
In the fluid flow layer (2), the pumping layer (3), the gas-powered layer (4) are PDMS material.
10. the device of bionical blood vessel network tumor-cell extravasation migration as described in any one of claim 1 to 9, feature exist
In, the supporting layer (1), the fluid flow layer (2), the pumping layer (3), the gas-powered layer (4) by based on etc.
The bonding technology of Ion Cleaning technology is assembled integrally.
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