WO2019178923A1

WO2019178923A1 - Fluid shear stress generation device and fluid shear stress generation method

Info

Publication number: WO2019178923A1
Application number: PCT/CN2018/085667
Authority: WO
Inventors: 陈华英; 陈畅; 朱永刚; 于志航
Original assignee: 哈尔滨工业大学深圳研究生院
Priority date: 2018-03-20
Filing date: 2018-05-04
Publication date: 2019-09-26
Also published as: CN108339580B; CN108339580A

Abstract

The present invention relates to the field of micro-fluidic chips. Disclosed are a fluid shear stress generation device and a fluid shear stress generation method. The device comprises a device body; a main flow passage and at least two branch flow passages are provided on the device body; the two ends of the main flow passage are provided with a fluid inlet and a main flow passage fluid outlet; one end of each branch flow passage is communicated with the main flow passage, and the other end is provided with a branch flow passage fluid outlet; valves capable of regulating cross sectional areas in the branch flow passages to allow fluid to pass through are provided in the branch flow passages. According to the present invention, by means of the cooperation of the main flow passage, the branch flow passages, and the valves, dynamic changes of the magnitudes and ratio of fluid shear stresses can be achieved without changing the flow velocity of input fluid and the structure of the device. In addition, the present invention can greatly expand the range of the ratio of the fluid shear stresses in first and final branch flow passages; moreover, the ratio at any point in the range can be covered. The device is simple in structure, and easy to popularize and implement.

Description

Fluid shear force generating device and fluid shear force generating method

Technical field

The invention relates to the field of microfluidic chips, in particular to a fluid shear force generating device capable of realizing a wide range and dynamic adjustment of fluid shearing force in a flow channel, and a fluid shearing force generating method.

Background technique

The body has a complex vascular system ranging in diameter from a few microns to a few centimeters. The fluid shear forces formed by blood flow in the veins and arteries are about 0.7-9 dyn/cm ² and 20-70 dyn/cm ^{2 , respectively} . Shear forces sometimes exceed 450 dyn/cm ² in narrow arterial vessels. Blood flow shear is closely related to a complex set of biological processes in the human body. Simulating this complex shearing environment in an in vitro model is important for the study of endothelial cell function, cardiovascular disease, and thrombosis.

As early as the 1980s, parallel plate flow chambers and cone and plate viscometer shear devices were used to study the effects of shear forces on endothelial cells and thrombosis. With the development of microfluidics, microfluidic chips can use internal integrated microvalves or external syringe pumps to generate continuous or pulsating fluid shear forces for more accurate simulation of shear forces generated by blood flow. Study the morphological changes, permeability, protein expression and transendothelial resistance of endothelial cells. Microfluidic chips have also been used to simulate the formation of stenotic vessels and thrombus. In addition, the microfluidic shear device can also be used to evaluate the effects of anti-stress drugs. These studies have greatly promoted basic research in endothelial cells, thrombosis and therapeutic research, and have played an important role in cardiovascular research and treatment.

Existing shearing force generating devices based on microfluidic chips mainly generate active fluid shearing forces in both active and passive ways. The active mode is mainly to change the inlet liquid flow rate to change the shear force in all the flow channels on the entire chip. Passive mode is to pre-design pipes of different lengths or widths on the chip to generate corresponding shear forces inside the liquid when it flows into different pipes. The above method is simple and easy, but it has great limitations, such as

(1) The magnitude of the fluid shear force in each flow path in the conventional shear force generating device is fixed without changing the input fluid velocity, and dynamic adjustment cannot be performed.

(2) The ratio of fluid shear force in different flow channels is fixed (linear distribution), and the ratio of fluid shear force in each flow channel cannot be dynamically adjusted without changing the chip design.

(3) It is impossible to produce all fluid shear forces covering the human vascular system. Therefore, existing microfluidic devices are difficult to accurately simulate a complex, wide range of fluid shearing environments within the human vasculature.

Summary of the invention

In order to overcome the deficiencies of the prior art, the present invention provides a fluid shear force generating device and a fluid shear force generating method for solving the existing shear force generating device 1) unable to simulate the internal fluid shear force of all blood vessels of the human body. The size and 2) can not dynamically adjust the size and ratio of fluid shear forces in each flow channel without changing the input fluid velocity.

The solution adopted by the present invention to solve its technical problems is:

A fluid shear force generating device comprises a device body, wherein a main channel and at least two branch flow channels are arranged on the main body, and a fluid inlet and a main channel fluid outlet are arranged at two ends of the main flow channel, and one end of the branch flow channel and the main flow The road is connected, and the other end is provided with a branch flow channel fluid outlet. The branch flow channel is provided with a valve for adjusting the cross-sectional area of the branch flow channel for the passage of the fluid.

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 be recessed toward the inside of the flow path.

As a further improvement of the above aspect, the pressing device applies pressure to the elastic diaphragm in one direction.

As a further improvement of the above aspect, the pressurizing means presses the elastic diaphragm in the circumferential direction of the branch flow path.

As a further improvement of the above aspect, the valve includes a magnetic elastic diaphragm constituting 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 recessed toward the inside of the flow path.

As a further improvement of the above scheme, the valve includes a magnetic bead injected into the branch flow path, and a magnetic device that applies a magnetic field to the magnetic bead to cause it to accumulate on the flow path wall in the branch flow path.

As a further improvement of the above aspect, the branch flow path includes an inlet region between the valve-to-branch flow path and the main flow path, and a shear force adjustment region disposed between the valve and the branch flow channel fluid outlet.

As a further improvement of the above scheme, each of the valves is independently adjusted or adjusted synchronously.

A method for generating a fluid shear force, comprising the following steps,

S10 is provided with a main flow channel having a fluid inlet and a main flow channel outlet, and at least two branch flow passages communicating with the main flow passage, the branch flow passage having a branch flow passage fluid outlet;

S20 is provided in each branch flow channel with a valve that can adjust the cross-sectional area of the branch flow channel;

S30 injects fluid into the main flow passage through the fluid inlet, and adjusts the respective valves to adjust the magnitude and ratio of the shear force in each branch flow passage.

As a further improvement of the above scheme, after the adjustment of each valve is completed, the flow velocity of the fluid in the main flow passage is adjusted to adjust the shear force amount while the shear force ratio in each branch flow passage remains unchanged.

The beneficial effects of the invention are:

The invention utilizes the cooperation of the main flow channel, the branch flow channel and the valve, and can realize the dynamic change of the fluid shear force magnitude and the ratio without changing the input fluid flow rate and the device structure. At the same time, the invention can greatly expand the ratio range of the fluid shear force in the first-stage and the last-stage branch flow channels, and can cover the ratio of any point in the range. The invention has a simple structure and is easy to popularize and realize.

DRAWINGS

The invention will now be further described with reference to the drawings and embodiments.

Figure 1 is a front elevational view of one embodiment of the present invention;

2 is a schematic diagram of analog resistance of a main flow path and a branch flow path of the present invention;

Figure 3 is a schematic view showing the waveform of the first embodiment of the shear flow ratio of each branch channel of the present invention;

Figure 4 is a schematic view showing the waveform of the second embodiment of the shear flow ratio of each branch channel of the present invention;

Figure 5 is a schematic view showing the waveform of the third embodiment of the shear flow ratio of each branch channel of the present invention;

Figure 6 is a schematic view showing the waveform of a fourth embodiment of the shear force ratio of each branch channel of the present invention;

Figure 7 is a schematic view of a first embodiment of the valve of the present invention;

Figure 8 is a schematic view of a second embodiment of the valve of the present invention;

Figure 9 is a schematic view of a third embodiment of the valve of the present invention;

Figure 10 is a schematic illustration of a fourth embodiment of the valve of the present invention.

detailed description

The concept, 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. It should be noted that the embodiments in the present application and the features in the embodiments may be combined with each other without conflict.

It should be noted that, unless otherwise stated, when a feature is referred to as “fixed” or “connected” in another feature, it may be directly fixed, connected to another feature, or indirectly fixed and connected to another feature. A feature. Further, the descriptions of the upper, lower, left, right, front, rear, and the like used in the present invention are only relative to the mutual positional relationship of the respective components of the present invention in the drawings.

Moreover, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art, unless otherwise defined. The terminology used in the description herein is for the purpose of description The term "and/or" used herein includes any combination of one or more of the associated listed items.

Referring to Figure 1, a front elevational view of one embodiment of the present invention is shown. As shown, the fluid shear force generating device includes a device body not shown. The device body is provided with a main flow channel 100 and at least two branch flow channels 200. Both ends of the main flow channel 100 are provided with a fluid inlet 101 and a main flow channel fluid. At the outlet 102, one end of the branch flow channel 200 is in communication with the main flow channel 100, and the other end is provided with a branch flow channel fluid outlet 201. Preferably, in this embodiment, the branch flow channels 200 are disposed on the same side of the main flow channel 100 and are parallel to each other.

The valve 300 is disposed in each branch flow channel 200 to adjust the cross-sectional area of the branch flow channel 200 for the passage of fluid. The valve 300 divides the branch flow channel 200 into two regions, which are respectively located at the valve 300. An inlet region 202 between the branch runner 200 and the main runner 100, and a shear force adjustment region 203 disposed between the valve 300 and the branch runner fluid outlet 201. By controlling each valve 300 independently or synchronously, the cross-sectional area of the branch flow path 200 at each valve 300 can be adjusted, thereby dynamically adjusting the shearing force of each branch flow path 200, and greatly expanding the variation range of the shear force. The implementation principle of the present invention is as follows:

Referring to Figure 2, there is shown a schematic diagram of the analog resistance of the main flow path and the branch flow path of the present invention. As shown in the figure, the main flow path and the branch flow path can be approximated as an analog circuit as shown in the figure, wherein the flow resistance of the flow path is analogized to the resistance in the electronic circuit, and R _m represents each branch flow path 200 and the main flow. The main flow path resistance between the junctions of the channels 100, Rs represents the flow resistance of the inlet region 202, R _v represents the flow resistance of the valve 300, and R _c represents the flow resistance of the shear force adjustment region 203.

Among them, for the non-valve area, the flow path section is rectangular (h<w), so the flow resistances R _m , R _s and R _c can be calculated by:

Calculated by calculation. Where μ represents the dynamic viscosity of the fluid, L represents the length of the runner, w represents the width of the runner, and h represents the height of the runner. Based on the above, it can be seen that when the fluid dynamic viscosity remains unchanged, the flow resistance of the non-valve region where the cross-sectional area does not change is constant.

For the valve area, the flow resistance R _{v of the} valve 300 is determined by the degree of deformation of the valve. For a micro flow path with several branch flow paths (assuming the total number of flow paths is n), it can be calculated from the last branch of the flow path. Outflow Q _n . The liquid flowing from the bifurcation is divided into two split streams, one to the outlet and the other to the last branch flow. The flow resistance of the flow path from the last branch to the outlet meets:

R(n)=R _m

The flow is inversely proportional to the flow resistance, so the relationship between the exit flow (q _n ) and the last branch flow (Q _n ) is:

among them:

R _b =R _s +R _v +R _c

Then, discuss it at the penultimate fork. The inlet flow rate of the first last branch port can be regarded as the exit flow rate (q _n-1 ) of the penultimate branching port, and the flow resistance of all the flow channels after the penultimate branching port meets:

The traffic distribution of the penultimate branch is satisfied:

By analogy, using iteration, we can get the divisor for the i-th (1 ≤ i ≤ n):

Among them, because

R(n)=R _m

And, the flow rate (Q _i ) of the i-th branch flow path inlet satisfies:

Therefore, the ratio of the flow rate in each branch flow path, that is, the flow rate ratio in the shear force adjustment region 203 in the present invention can be obtained from the above formula. Further based on the shear force formula in a square pipe:

The shear force ratio in the varying region of each branch flow path can be found. Where μ represents the fluid dynamic viscosity, Q represents the volumetric flow 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 known from the above formula that it is only necessary to change the flow resistance R _v of the valve of each flow channel to realize the change of the flow relationship in each branch flow channel, thereby generating a change in the shear force relationship even if the flow rate of the input fluid The same can be achieved, the dynamic adjustment of the shear force can also be achieved.

The present invention does not limit the number of branch flow passages 200, and the number thereof is adjusted according to the adjustment range of the shearing force. The larger the number of branch flow passages 200, the larger the variation range. Referring to Table 1, the theoretically calculated maximum shear stress variation range is shown. Relationship with the number of branch runners:

Table 1 Ratio of fluid shear force in the first and last flow channels when the number of total branch channels changes

It can be seen from the above table that when 8 branch flow channels are provided, the ratio of fluid shear force in the first and last branch flow passages can reach 18509:1 by adjusting the valve, and the flow resistance deformation in the valve region is continuous. Therefore, the flow resistance can also be continuously changed, that is, the present invention can cover the ratio of the shear stress value at any point within the range.

When the magnitude of the cross-sectional area of a certain branch flow path 200 is changed, the magnitude and ratio of the shear forces in all of the branch flow paths 200 change. By precisely controlling the degree of closure of the valve 300 in each branch flow channel 200, dynamic switching of the numerical distribution of fluid shear forces in each branch flow channel 200 between linear, exponential and sinusoidal conditions can be achieved.

Referring to Table 2, a diaphragm type valve is taken as an example to show a combination of the amount of deformation of each branch flow path (setting the deformation amount of the diaphragm in the first branch flow path to be a):

Table 2 Deformation of each branch runner valve required to achieve a specific shear force distribution

When the branch flow paths are respectively combined by the deformation amounts listed in the table, the values of the fluid shear forces in the respective branch flow paths 200 are distributed as shown in FIGS. 3 to 6.

The valve of the present invention is used to adjust the cross-sectional area of the branch flow path 200. Referring to Figures 7 through 10, schematic views of different embodiments of the valve of the present invention are shown, respectively. 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 pressing device that applies pressure to the elastic diaphragm 301 to be recessed toward the inside of the flow path (not shown). After the pressure is applied by the pressing device, the cross-sectional area of the branch flow path 200 is reduced. When the pressure is removed, the elastic diaphragm 301 is restored by its own elastic force, and the cross-sectional area of the branch flow path 200 is restored.

The pressure device can be used in the prior art, such as a pneumatic drive device, a hydraulic drive device, etc., which is not limited by the present invention.

The pressing method of the present invention is not limited. For example, as shown in FIG. 7, the pressing device may apply unidirectional pressure to the elastic diaphragm 301, or may be elastic along the circumferential direction of the branch flow passage 200 as shown in FIG. The diaphragm 302 is multi-directionally pressed.

As shown in Fig. 9, the valve 300 includes a magnetic elastic diaphragm 303 constituting a flow path wall of the branch flow path 200, and a magnetic device 401 that applies a magnetic field to the elastic diaphragm 303 to attract it to the inside of the flow path. The magnetic elastic film referred to herein may be either the magnetic film 303 itself has magnetic properties, or the magnetic film 303 may be additionally fixed with magnetic components. In addition, the term "magnetic" as used herein can be understood as being capable of actively adsorbing other components, and can also be understood as being capable of being adsorbed by other components.

As shown in FIG. 10, valve 300 includes magnetic beads 304 that are injected into the branch flow channels, and magnetic devices 402 that apply magnetic fields to magnetic beads 304 to build up on the flow path walls within the branch flow channels. As the magnetic field increases and decreases, the magnetic beads 304 adsorbed on the walls of the flow path increase and decrease accordingly.

The magnetic member in this embodiment is preferably an electromagnet so as to be able to dynamically adjust the magnetic size.

In addition to the above embodiments, other known valve structures may be employed in the present invention, and the present invention is not limited thereto.

The invention also discloses a fluid shear force generating method, comprising the following steps,

S10 is provided with a main flow path having a fluid inlet and a main flow channel outlet, and at least two branch flow paths communicating with the main flow path are provided, and the branch flow path has a branch flow path fluid outlet.

S20 is provided in each branch flow channel to adjust the cross-sectional area of the branch flow channel, and the valve here can adopt the valve structure in the above embodiment.

Further, after the adjustment of each of the above valves is completed, the flow rate of the fluid in the main flow channel can be adjusted to adjust the shear force amount while the shear force ratio in each branch flow path remains unchanged.

The above is a detailed description of the preferred embodiments of the present invention, but the present invention is not limited to the embodiments, and various equivalent modifications or substitutions can be made by those skilled in the art without departing from the spirit of the invention. Such equivalent modifications or alternatives are intended to be included within the scope of the claims.

Claims

A fluid shear force generating device, comprising: a device body, wherein the device body is provided with a main flow channel and at least two branch flow channels, and both ends of the main flow channel are provided with a fluid inlet and a main flow channel fluid outlet One end of the branch flow channel is in communication with the main flow channel, and the other end is provided with a branch flow channel fluid outlet, and the branch flow channel is provided with a valve that can adjust a cross-sectional area of the branch flow channel through which the fluid can pass.
A fluid shear force generating apparatus according to claim 1, wherein said valve includes an elastic diaphragm constituting a flow path wall of said branch flow path, and applying pressure to said elastic diaphragm to cause A pressing device that is recessed inside the flow path.
The fluid shear force generating apparatus according to claim 2, wherein said pressurizing means presses said elastic diaphragm in a one-sided direction.
The fluid shear force generating apparatus according to claim 2, wherein said pressurizing means applies pressure to said elastic diaphragm in a circumferential direction of said branch flow path.
A fluid shear force generating apparatus according to claim 1, wherein said valve comprises a magnetic elastic diaphragm constituting a flow path wall of said branch flow path, and a magnetic field is applied to said elastic diaphragm The magnetic device that attracts it to the inside of the flow channel is attracted.
A fluid shear force generating apparatus according to claim 1, wherein said valve includes a magnetic bead injected into said branch flow path, and a magnetic field is applied to said magnetic bead to be within said branch flow path A magnetic device that accumulates on the wall of the flow channel.
The fluid shear force generating apparatus according to claim 1, wherein said branch flow path includes an inlet region between said valve to said branch flow path and said main flow path, and is provided at a shear force adjustment region between the valve and the branch flow channel fluid outlet.
The fluid shear force generating apparatus according to claim 1, wherein each of said valves is independently adjusted or adjusted in synchronization.
A method for generating a fluid shear force, comprising the following steps,

S10 is provided with a main flow channel having a fluid inlet and a main flow channel outlet, and at least two branch flow passages communicating with the main flow passage, the branch flow passage having a branch flow passage fluid outlet;

S20 is provided in each branch flow channel with a valve that can adjust the cross-sectional area of the branch flow channel;

S30 injects fluid into the main flow passage through the fluid inlet, and adjusts the magnitude and ratio of shear forces in each of the branch flow passages by adjusting each of the valves.
The fluid shear force generating method according to claim 9, wherein after the adjustment of each of the valves is completed, the flow velocity of the fluid in the main flow passage is adjusted to maintain a shear force ratio in each of the branch flow passages. Adjust the amount of shear force under constant conditions.