WO2019178923A1 - Dispositif de génération de contrainte de cisaillement de fluide et méthode de génération de contrainte de cisaillement de fluide - Google Patents

Dispositif de génération de contrainte de cisaillement de fluide et méthode de génération de contrainte de cisaillement de fluide Download PDF

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Publication number
WO2019178923A1
WO2019178923A1 PCT/CN2018/085667 CN2018085667W WO2019178923A1 WO 2019178923 A1 WO2019178923 A1 WO 2019178923A1 CN 2018085667 W CN2018085667 W CN 2018085667W WO 2019178923 A1 WO2019178923 A1 WO 2019178923A1
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Prior art keywords
fluid
branch flow
shear force
branch
flow channel
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PCT/CN2018/085667
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English (en)
Chinese (zh)
Inventor
陈华英
陈畅
朱永刚
于志航
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哈尔滨工业大学深圳研究生院
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Publication of WO2019178923A1 publication Critical patent/WO2019178923A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502776—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for focusing or laminating flows
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G01N33/4915—Blood using flow cells
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/082—Active control of flow resistance, e.g. flow controllers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves

Definitions

  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • the pressing device applies pressure to the elastic diaphragm in one direction.
  • the pressurizing means presses the elastic diaphragm in the circumferential direction of the branch flow path.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 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.
  • Figure 1 is a front elevational view of one embodiment of the present invention
  • FIG. 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.
  • 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.
  • 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.
  • 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.
  • FIG. 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.
  • 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 flow path section is rectangular (h ⁇ w), so the flow resistances R m , R s and R c can be calculated by:
  • 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 b R s +R v +R c
  • 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 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.
  • ⁇ 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
  • h represents the height of the flow channel.
  • 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 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.
  • 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):
  • the valve of the present invention is used to adjust the cross-sectional area of the branch flow path 200.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Ecology (AREA)
  • Magnetically Actuated Valves (AREA)
  • Micromachines (AREA)

Abstract

La présente invention concerne le domaine des puces microfluidiques. L'invention concerne un dispositif de génération de contrainte de cisaillement de fluide et une méthode de génération de contrainte de cisaillement de fluide. Le dispositif comprend un corps de dispositif ; un passage d'écoulement principal et au moins deux passages d'écoulement de dérivation sont prévus sur le corps de dispositif ; les deux extrémités du passage d'écoulement principal sont pourvues d'une entrée de fluide et d'une sortie de fluide de passage d'écoulement principal ; une extrémité de chaque passage d'écoulement de dérivation est en communication avec le passage d'écoulement principal, et l'autre extrémité est pourvue d'une sortie de fluide de passage d'écoulement de dérivation ; des vannes capables de réguler des zones de section transversale dans les passages d'écoulement de dérivation pour permettre à un fluide de passer à travers celles-ci sont prévues dans les passages d'écoulement de dérivation. Selon la présente invention, au moyen de la coopération du passage d'écoulement principal, des passages d'écoulement de dérivation et des vannes, des changements dynamiques des amplitudes et du rapport des contraintes de cisaillement de fluide peuvent être obtenus sans changer la vitesse d'écoulement du fluide d'entrée et la structure du dispositif. De plus, la présente invention peut considérablement étendre la plage du rapport des contraintes de cisaillement de fluide dans un premier passage et un passage final d'écoulement de dérivation ; en outre, le rapport à n'importe quel point dans la plage peut être couvert. Le dispositif est simple en structure et facile à populariser et à mettre en œuvre.
PCT/CN2018/085667 2018-03-20 2018-05-04 Dispositif de génération de contrainte de cisaillement de fluide et méthode de génération de contrainte de cisaillement de fluide WO2019178923A1 (fr)

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CN201810228424.1 2018-03-20
CN201810228424.1A CN108339580B (zh) 2018-03-20 2018-03-20 一种流体剪切力生成装置与流体剪切力生成方法

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CN112916062A (zh) * 2021-01-29 2021-06-08 哈尔滨医科大学 微流控芯片液体流动的驱动方法
CN113671165B (zh) * 2021-08-23 2023-06-20 哈尔滨工业大学（深圳） 一种用于活细胞力学性能高通量精密检测的装置及方法

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CN102787071A (zh) * 2012-07-27 2012-11-21 中国科学院大连化学物理研究所 基于微流控芯片系统的模拟体内流体剪切力细胞行为研究
CN102816695A (zh) * 2011-06-08 2012-12-12 大连医科大学 一种微流控芯片及其研究流体剪切力对细胞作用的方法
WO2016004394A1 (fr) * 2014-07-03 2016-01-07 Texas Tech University System Procédé et système cardiovasculaires microfluidiques
CN105910847A (zh) * 2016-04-01 2016-08-31 清华大学深圳研究生院 一种取液量可调的疏液微阀式微量液体提取装置与方法
CN107051599A (zh) * 2017-05-15 2017-08-18 深圳先进技术研究院 微流控芯片及微流控芯片控制方法

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CN208194421U (zh) * 2018-03-20 2018-12-07 哈尔滨工业大学深圳研究生院 一种流体剪切力生成装置

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102816695A (zh) * 2011-06-08 2012-12-12 大连医科大学 一种微流控芯片及其研究流体剪切力对细胞作用的方法
CN102787071A (zh) * 2012-07-27 2012-11-21 中国科学院大连化学物理研究所 基于微流控芯片系统的模拟体内流体剪切力细胞行为研究
WO2016004394A1 (fr) * 2014-07-03 2016-01-07 Texas Tech University System Procédé et système cardiovasculaires microfluidiques
CN105910847A (zh) * 2016-04-01 2016-08-31 清华大学深圳研究生院 一种取液量可调的疏液微阀式微量液体提取装置与方法
CN107051599A (zh) * 2017-05-15 2017-08-18 深圳先进技术研究院 微流控芯片及微流控芯片控制方法

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