CN108339580B - Fluid shear force generation device and fluid shear force generation method - Google Patents

Fluid shear force generation device and fluid shear force generation method Download PDF

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CN108339580B
CN108339580B CN201810228424.1A CN201810228424A CN108339580B CN 108339580 B CN108339580 B CN 108339580B CN 201810228424 A CN201810228424 A CN 201810228424A CN 108339580 B CN108339580 B CN 108339580B
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flow channel
fluid
branch flow
shear force
branch
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CN108339580A (en
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陈华英
陈畅
朱永刚
于志航
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Shenzhen Graduate School Harbin Institute of Technology
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Abstract

The invention relates to the field of microfluidic chips, and discloses a fluid shear force generation device and a fluid shear force generation method, wherein the device comprises a device main body, a main flow channel and at least two branch flow channels are arranged on the device main body, a fluid inlet and a main flow channel fluid outlet are arranged at two ends of the main flow channel, one end of each branch flow channel is communicated with the main flow channel, a branch flow channel fluid outlet is arranged at the other end of each branch flow channel, a valve is arranged in each branch flow channel, and the cross section area through which fluid can pass in each branch flow channel is adjusted by controlling the closing degree of the valve. The invention can realize dynamic change of the shearing force and the ratio of the fluid under the condition of not changing the flow speed of the input fluid and the structure of the device by utilizing the matching of the main flow channel, the branch flow channel and the valve. Meanwhile, the invention can greatly expand the ratio range of the fluid shearing force in the first-stage branch flow passage and the last-stage branch flow passage, and can cover the ratio of any point in the range.

Description

Fluid shear force generation device and fluid shear force generation method
Technical Field
The invention relates to the field of microfluidic chips, in particular to a fluid shear force generation device and a fluid shear force generation method, which can realize large-range and dynamic adjustment of fluid shear force in a flow channel.
Background
The body has a complex vascular system, ranging in diameter from a few microns to a few centimeters. The fluid shear forces generated by blood flow in the venous and arterial vessels are about 0.7-9dyn/cm, respectively2And 20-70dyn/cm2. Shear forces in stenotic arterial vessels sometimes exceed 450dyn/cm2. The blood flow shear force is closely related to a series of complex biological processes in the human body. The simulation of the complex shear force environment in an in vitro model has important significance for the research of endothelial cell functions, cardiovascular diseases, thrombus and the like.
As early as the 80's of the last century, parallel plate flow chamber and cone and plate viscometer shear devices were used to study the effect of shear on endothelial cells and thrombus formation. With the development of microfluidic technology, the microfluidic chip can generate continuous or pulsating fluid shear force by using an internally integrated micro valve or an external syringe pump, so as to more accurately simulate the shear force generated by blood flow, and further study the morphological change, permeability, protein expression, transendothelial resistance and the like of endothelial cells. Microfluidic chips have also been used to simulate the formation of stenotic vessels and thromboplastin. In addition, microfluidic shear force devices can also be used to assess the effect of anti-stress drugs. These studies have greatly promoted the fundamental research on endothelial cells, the research on thrombosis and the research on treatment, and have important effects on the research and treatment of cardiovascular diseases.
The existing shear force generating device based on the micro-fluidic chip mainly adopts an active mode and a passive mode to generate variable fluid shear force. The active mode is mainly to change the flow rate of the inlet liquid so as to change the shearing force in all the flow channels on the whole chip. The passive mode is to pre-design channels with different lengths or widths on the chip, and when liquid flows into different channels, corresponding shearing force is generated inside the channels. The above methods, while simple to implement, have significant limitations, e.g.
(1) In the conventional shear force generating device, the magnitude of the fluid shear force in each flow channel is fixed without changing the speed of the input fluid, and dynamic adjustment cannot be performed.
(2) The ratio of the fluid shear forces in different flow channels is fixed (linearly distributed), and the ratio of the fluid shear forces in each flow channel cannot be dynamically adjusted on the premise of not changing the design of a chip.
(3) It is not possible to generate all the fluid shear forces within the human vascular system.
Therefore, it is difficult for the existing microfluidic devices to accurately simulate complex, wide-range fluid shear force environments within the human vascular system.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a fluid shear force generation device and a fluid shear force generation method, which are used for solving the problems that the conventional shear force generation device 1) cannot simulate the magnitude of fluid shear force in all blood vessels of a human body and 2) cannot dynamically adjust the magnitude and ratio of the fluid shear force in each flow channel under the condition of not changing the speed of input fluid.
The technical scheme adopted by the invention for solving the technical problems is as follows:
the utility model provides a fluid shear force generates device, includes the device main part, is provided with sprue and two at least branch runners in the device main part, and the both ends of sprue are provided with fluid inlet and sprue fluid outlet, and branch runner's one end and sprue intercommunication, the other end are equipped with branch runner fluid outlet, are equipped with the valve in the branch runner, can supply the sectional area that the fluid passes through in this branch runner through the closed degree regulation of control valve.
As a further improvement of the above aspect, the valve includes an elastic diaphragm constituting a flow path wall of the branch flow path, and a pressurizing means for applying pressure to the elastic diaphragm to cause it to be depressed toward the inside of the flow path.
As a further improvement of the above, the pressurizing means pressurizes the elastic membrane in a single-sided direction.
As a further improvement of the above aspect, the pressurizing means pressurizes the elastic membrane in the circumferential direction of the branch flow passage.
As a further improvement of the above aspect, the valve includes an elastic diaphragm having magnetism that constitutes a flow path wall of the branch flow path, and a magnetic device that applies a magnetic field to the elastic diaphragm to attract it to be depressed toward the inside of the flow path.
As a further improvement of the above aspect, the valve includes a magnetic bead injected into the branch flow channel, and a magnetic device that applies a magnetic field to the magnetic bead to cause it to accumulate on a flow channel wall in the branch flow channel.
As a further improvement of the above aspect, the branch flow passage includes an inlet region located between the valve and where the branch flow passage communicates with the main flow passage, and a shear force adjusting region provided between the valve and the fluid outlet of the branch flow passage.
As a further improvement of the above solution, each of the valves is adjusted independently or simultaneously.
A fluid shear force generation method includes the following steps,
s10, arranging a main flow channel with a fluid inlet and a main flow channel fluid outlet, and arranging at least two branch flow channels communicated with the main flow channel, wherein each branch flow channel is provided with a branch flow channel fluid outlet;
s20, arranging a valve capable of adjusting the sectional area of each branch flow passage in each branch flow passage;
s30 is to inject the fluid into the main channel through the fluid inlet, and adjust the closing degree of each valve to adjust the magnitude and ratio of the shearing force in each branch channel.
As a further improvement of the above solution, after the valves are adjusted, the flow rate of the fluid in the main flow channel is adjusted to adjust the magnitude of the shearing force while the ratio of the shearing force in the branch flow channels is kept unchanged.
The invention has the beneficial effects that:
the invention can realize dynamic change of the shearing force and the ratio of the fluid under the condition of not changing the flow speed of the input fluid and the structure of the device by utilizing the matching of the main flow channel, the branch flow channel and the valve. Meanwhile, the invention can greatly expand the ratio range of the fluid shearing force in the first-stage branch flow passage and the last-stage branch flow passage, and can cover the ratio of any point in the range.
Drawings
The invention is further illustrated with reference to the following figures and examples.
FIG. 1 is a front view of one embodiment of the present invention;
FIG. 2 is a schematic diagram of an analog resistance of the main flow channel and the branch flow channels according to the present invention;
FIG. 3 is a waveform illustrating the shear force ratio of the branch flow channels according to the first embodiment of the present invention;
FIG. 4 is a waveform illustrating a shear ratio of a branch flow channel according to a second embodiment of the present invention;
FIG. 5 is a waveform illustrating shear force ratios of the branched flow paths according to a third embodiment of the present invention;
FIG. 6 is a waveform illustrating a shear ratio of a branch flow passage according to a fourth embodiment of the present invention;
FIG. 7 is a schematic view of a first embodiment of the valve of the present invention;
FIG. 8 is a schematic view of a second embodiment of the valve of the present invention;
FIG. 9 is a schematic view of a third embodiment of the valve of the present invention;
figure 10 is a schematic view of a fourth embodiment of the valve of the present invention.
Detailed Description
The conception, the specific structure and the technical effects of the present invention will be clearly and completely described in conjunction with the embodiments and the accompanying drawings to fully understand the objects, the schemes and the effects of the present invention. It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict.
It should be noted that, unless otherwise specified, when a feature is referred to as being "fixed" or "connected" to another feature, it may be directly fixed or connected to the other feature or indirectly fixed or connected to the other feature. Furthermore, the descriptions of up, down, left, right, front, rear, etc. used in the present invention are only relative to the positional relationship of the respective components of the present invention with respect to each other in the drawings.
Furthermore, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The terminology used in the description herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any combination of one or more of the associated listed items.
Referring to FIG. 1, a front view of one embodiment of the present invention is shown. As shown in the figure, the fluid shear force generating device includes a device body, not shown, on which a main flow channel 100 and at least two branch flow channels 200 are disposed, a fluid inlet 101 and a main flow channel fluid outlet 102 are disposed at both ends of the main flow channel 100, one end of the branch flow channel 200 is communicated with the main flow channel 100, and the other end is disposed with a branch flow channel fluid outlet 201. Preferably, the branch channels 200 are disposed on the same side of the main channel 100 and are parallel to each other in this embodiment.
In the present invention, each branch flow channel 200 is provided with a valve 300 capable of adjusting a cross-sectional area of the branch flow channel 200 through which a fluid can pass, the valve 300 divides the branch flow channel 200 into two regions, namely an inlet region 202 located between the valve 300 and a connection portion between the branch flow channel 200 and the main flow channel 100, and a shear force adjusting region 203 located between the valve 300 and the branch flow channel fluid outlet 201. By independently or synchronously controlling the valves 300, the sectional area of the branch flow channel 200 at each valve 300 can be adjusted, so that the shearing force of each branch flow channel 200 is dynamically adjusted, and the variation range of the shearing force is greatly expanded, wherein the realization principle of the invention is as follows:
referring to fig. 2, an analog resistance diagram of the main flow channel and the branch flow channel of the present invention is shown. As shown, the main channel and the branch channels can be approximately regarded as analog circuits shown in the figure, in which the flow resistance of the channels is analog to the resistance, R, in the electronic circuitmDenotes a main flow channel flow resistance, R, between each junction of the branch flow channels 200 and the main flow channel 100sIndicating the flow resistance, R, of the inlet region 202vDenotes the flow resistance, R, of the valve 300cIndicating the flow resistance of the shear force modulation region 203.
Wherein, for the non-valve area, the cross section of the flow channel is rectangular (h)<w) so that the flow resistance R ism、RsAnd RcCan be represented by the formula:
Figure GDA0002143663040000071
and (6) calculating to obtain. Where μ represents the dynamic viscosity of the fluid, L represents the channel length, w represents the channel width, and h represents the channel height. Based on the above, it can be seen that the flow resistance of the non-valve region, in which the cross-sectional area does not change, is a constant value while the dynamic viscosity of the fluid remains unchanged.
Flow resistance R of valve 300 for valve areavThen, depending on the degree of valve deformation, for a microchannel with several branched channels (assuming that the total number of the fractional channels is n), the flow rate Q can be calculated from the last branch of the channeln. The liquid flowing out of the bifurcation is divided into two partial flows, one flowing to the outlet,the other to the final branching flow channel. The flow resistance of the flow path from the last bifurcation to the outlet satisfies:
R(n)＝Rm
and the flow rate is inversely proportional to the flow resistance, so the outlet flow rate (q)n) And last branch flow (Q)n) The relationship between them satisfies:
Figure GDA0002143663040000081
wherein:
Rb＝Rs+Rv+Re
then, discussion is made at the penultimate bifurcation. The inlet flow of the penultimate branch can be regarded as the outlet flow of the penultimate branch (q)n-1) And the flow resistance of all the flow passages after the penultimate fork meets the following requirements:
Figure GDA0002143663040000082
the flow distribution of the penultimate fork meets the following conditions:
by analogy, by utilizing iteration, the i (i is more than or equal to 1 and less than or equal to n) th fork can be obtained:
wherein, due to
R(n)＝Rm
And the flow rate (Q) of the ith branch flow passage inleti) Satisfies the following conditions:
Figure GDA0002143663040000085
the flow ratio in each branched flow channel, i.e., the flow ratio in the shear force adjusting region 203 in the present invention, can be obtained by the above formula. Further according to the formula of the shearing force in the square pipeline:
Figure GDA0002143663040000086
the shear force ratio in the varying region of each branch flow channel can be found. Where μ represents the dynamic viscosity of the fluid, Q represents the volumetric flow rate of the fluid in the flow channel, w represents the width of the flow channel, and h represents the height of the flow channel. In summary, it can be seen from the above formula that only the flow resistance R of the valve of each flow channel needs to be changedvTherefore, the change of the flow relation in each branch flow channel can be realized, the change of the shearing force relation is further generated, and the dynamic adjustment of the shearing force can be realized even if the flow speed of the input fluid is not changed.
The number of the branch flow channels 200 is not limited, the number of the branch flow channels is adjusted according to the adjusting range of the shearing force, the larger the number of the branch flow channels 200 is, the larger the change range is, and the relation between the maximum change range of the shear stress and the number of the branch flow channels, which is theoretically calculated, is shown with reference to table 1:
TABLE 1 ratio of fluid shear forces in the first and last flow channels when the number of total branch channels changes
Figure GDA0002143663040000091
It can be seen from the above table that when 8 branch flow channels are provided, by adjusting the valve, the ratio of the fluid shear forces in the first-stage and last-stage branch flow channels can reach 18509:1, and because the flow resistance deformation of the valve area is continuous, the flow resistance can also be continuously changed, i.e. the ratio of the shear stress value of any point in the coverage area of the invention can be realized.
When the size of the cross-sectional area of a certain branch flow path 200 is changed, the size and ratio of the shear force in all the branch flow paths 200 are changed. By precisely controlling the closing degree of the valve 300 in each branch flow channel 200, the dynamic switching of the distribution of the fluid shear force values in each branch flow channel 200 among the laws of linearity, exponential, sine, etc. can be realized.
Referring to table 2, taking a diaphragm valve as an example, a combination of the diaphragm deformation amounts of the respective branch flow channels is shown (the diaphragm deformation amount in the first branch flow channel is set to a):
TABLE 2 amount of valve deflection for each branch flow path required to achieve a particular shear force profile
Figure GDA0002143663040000101
When the combinations of the deformation amounts listed in the tables are respectively used for the branch flow channels, the values of the fluid shear forces in the branch flow channels 200 are distributed as shown in fig. 3 to 6.
The valve of the present invention is used to adjust the sectional area of the branched flow path 200, and referring to fig. 7 to 10, schematic diagrams of different embodiments of the valve of the present invention are respectively shown. Specifically, as shown in fig. 7, the valve 300 includes an elastic diaphragm 301 constituting a flow path wall of the branch flow path 200, and a pressurizing means (not shown) for applying a pressure to the elastic diaphragm 301 to recess it toward the flow path interior, and when the pressure is applied by the pressurizing means, the sectional area of the branch flow path 200 is reduced, and when the pressure is removed, the elastic diaphragm 301 is restored by its own elastic force, and the sectional area of the branch flow path 200 is restored therewith.
The pressurizing device may be a pneumatic driving device, a hydraulic driving device, etc., and the present invention is not limited thereto.
The pressing method of the present invention is not limited, and for example, the pressing device may press the elastic membrane 301 in one direction as shown in fig. 7, or may press the elastic membrane 302 in multiple directions along the circumferential direction of the branched flow path 200 as shown in fig. 8.
As shown in fig. 9, the valve 300 includes an elastic diaphragm 303 having magnetism constituting a flow channel wall of the branched flow channel 200, and a magnetic device 401 applying a magnetic field to the elastic diaphragm 303 to attract it to be depressed toward the inside of the flow channel. The elastic diaphragm 303 with magnetism may be magnetic itself, or a magnetic component may be additionally fixed on the elastic diaphragm 303. In addition, the term "magnetic" as used herein is understood to mean either being capable of actively attracting another component or being attracted by another component.
As shown in fig. 10, the valve 300 includes a magnetic bead 304 injected into the branch flow channel, and a magnetic device 402 applying a magnetic field to the magnetic bead 304 to be accumulated on the wall of the flow channel in the branch flow channel. As the magnetic field increases and decreases, the magnetic beads 304 attached to the walls of the flow channel also increase and decrease accordingly.
The magnetic component in this embodiment is preferably an electromagnet so that the magnetic magnitude can be dynamically adjusted.
In addition to the above embodiments, the present invention may also adopt other known valve structures, and the present invention is not limited thereto.
The invention also discloses a fluid shear force generation method, which comprises the following steps,
s10 includes a main flow channel having a fluid inlet and a main flow channel fluid outlet, and at least two branch flow channels communicating with the main flow channel, the branch flow channels having branch flow channel fluid outlets.
S20, setting a valve capable of adjusting the cross-sectional area of each branch flow passage in each branch flow passage, wherein the valve can adopt the valve structure in the above-mentioned embodiment.
S30 injecting fluid into the main channel through the fluid inlet, and adjusting the valves to adjust the magnitude and ratio of the shear force in the branch channels.
Furthermore, after the valves are adjusted, the flow rate of the fluid in the main flow channel can be adjusted, so that the shearing force can be adjusted while the shearing force ratio in each branch flow channel is kept unchanged.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims (10)

1. The fluid shear force generation device based on the micro-fluidic chip is characterized by comprising a device main body, wherein a main flow channel and at least two branch flow channels are arranged on the device main body, a fluid inlet is formed in one end of the main flow channel, a main flow channel fluid outlet is formed in the other end of the main flow channel, one ends of the branch flow channels are communicated with the main flow channel, branch flow channel fluid outlets are formed in the other ends of the branch flow channels, valves are arranged in the branch flow channels, and the cross-sectional areas, through which fluids can pass, in the branch flow channels are adjusted by controlling the closing degree of the valves.
2. The fluid shear force generating device according to claim 1, wherein the valve comprises an elastic diaphragm constituting a flow path wall of the branch flow path, and a pressurizing means for applying a pressure to the elastic diaphragm to cause it to be depressed toward the inside of the flow path.
3. The fluid shear force generating device of claim 2, wherein the pressurizing means pressurizes the elastic membrane in a single-sided direction.
4. The fluid shear force generating device according to claim 2, wherein the pressurizing means pressurizes the elastic membrane in the circumferential direction of the branch flow passage.
5. The fluid shear force generating device according to claim 1, wherein the valve comprises an elastic diaphragm having magnetism constituting a flow channel wall of the branched flow channel, and a magnetic means for applying a magnetic field to the elastic diaphragm to attract it to be depressed toward the inside of the flow channel.
6. The apparatus according to claim 1, wherein the valve comprises a magnetic bead injected into the branch flow channel, and a magnetic device for applying a magnetic field to the magnetic bead to cause the magnetic bead to accumulate on a wall of the flow channel in the branch flow channel.
7. The fluid shear force generating device according to claim 1, wherein the branch flow passage includes an inlet region between the valve to where the branch flow passage communicates with the main flow passage, and a shear force adjusting region provided between the valve to a fluid outlet of the branch flow passage.
8. A fluid shear force generating device according to claim 1, wherein each of the valves is adjusted independently or simultaneously.
9. A fluid shear force generation method based on a microfluidic chip comprises the following steps,
s10, arranging a main flow channel with a fluid inlet and a main flow channel fluid outlet, and arranging at least two branch flow channels communicated with the main flow channel, wherein the branch flow channels are provided with branch flow channel fluid outlets;
s20, arranging a valve capable of adjusting the sectional area of each branch flow passage in each branch flow passage;
s30, injecting a fluid into the main channel through the fluid inlet, and adjusting the degree of closure of each valve to adjust the magnitude and ratio of the shear force in each branch channel.
10. A method for generating a shear force in a fluid according to claim 9, wherein after the valves are adjusted, the flow rate of the fluid in the main flow channel is adjusted to adjust the magnitude of the shear force while the ratio of the shear force in each of the branch flow channels is kept constant.
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