CN114558631B - Microfluidic device, microfluidic sample input system and control method - Google Patents

Microfluidic device, microfluidic sample input system and control method Download PDF

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CN114558631B
CN114558631B CN202210266418.1A CN202210266418A CN114558631B CN 114558631 B CN114558631 B CN 114558631B CN 202210266418 A CN202210266418 A CN 202210266418A CN 114558631 B CN114558631 B CN 114558631B
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sample
liquid
storage container
microfluidic
flow
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CN114558631A (en
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杨志辉
黎佳未
颜旭
胡文吉豪
廖骐
王庆伟
王海鹰
阳钰玮
朱德懿
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Central South University
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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
    • B01L3/50273—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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • 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
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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

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  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

The invention provides a microfluidic sample input system suitable for non-neutral buoyancy particles, which comprises a sample storage assembly, a constant-pressure air pump and a control end, wherein the sample storage assembly comprises a sample storage tank, a sample storage tank and a sample output port; the sample storage assembly comprises a sample storage container and a suspension mechanism; the air pressure output end of the constant pressure air pump is communicated with the air inlet end of the sample storage container through an air conduit, and the air inlet end of the sample storage container is higher than the liquid storage height; the sample storage container is communicated with the microfluidic device through a liquid guide pipe, a liquid inlet end of the liquid guide pipe extends into a liquid storage range, a flow sensor is arranged on the liquid guide pipe, and the flow sensor is in communication connection with the control end; the control end is in communication connection with the constant-pressure air pump so as to control the flow of the sample liquid according to the information fed back by the flow sensor. The invention can lead the non-neutrally buoyant particles to stably circulate in the microfluidic system at a controllable flow rate, and has stronger applicability and universality compared with the traditional microfluidic control method and technology.

Description

Microfluidic device, microfluidic sample input system and control method
Technical Field
The invention relates to the technical field of microfluidics, in particular to a microfluidic device, a microfluidic sample input system and a control method.
Background
In recent years, the microfluidic technology is rapidly developed, and has attracted extensive attention due to the characteristics of continuous operation, safety and high sorting precision. The current microfluidic technology is applied to pretreatment of neutral buoyancy particle (density is equivalent to water) samples, and comprises sorting and concentration of blood cells, cancer cells, microorganisms and the like. Meanwhile, there have been many applications to couple microfluidic cell concentration and sorting techniques with downstream characterization techniques to achieve rapid or in situ analysis of cells.
Microfluidics mainly realizes the functions of concentration, separation and the like of particles through the characteristic of flowing under a microscale. The operating platform of the microfluidic technology comprises three parts: sample input systems, microfluidic devices, and downstream collection or analysis systems. The sample input system is mainly used for controlling the flow rate to input samples into the microfluidic device so as to realize controllable microfluidic characteristics. The micro-fluidic device mainly realizes the functions of concentration or separation and the like through a customized micron-sized pipeline. Downstream collection or analysis systems are storage or rapid analysis of samples processed by microfluidic technology. Although the microfluidic device is a core link for realizing success of concentration or sorting, the sample input system is an important prerequisite for ensuring the function of the microfluidic device, and if the sample input system cannot enable the sample to be in a stable microfluidic state, the whole microfluidic system will inevitably fail. The current sample input system usually adopts sampling devices such as peristaltic pumps, injection pumps and the like, can ensure the suspension and stable circulation of neutral buoyancy particles, obtains better effect and is widely applied.
Micro-nano particles in an environmental medium are ubiquitous, and numerous reports prove that the micro-nano particles in solid waste, soil and smoke dust are important influence factors influencing the toxicity, the mobility and the pollution treatment effectiveness of the micro-nano particles. Based on the important application potential of micro-fluidic in the aspects of micro-nano particle sorting and micro-characterization, whether the technology can be applied to the aspects of solid waste, soil, smoke dust and the like needs to be explored urgently, and an important path can be provided for the analysis and characterization of the samples and the separation and treatment of the polluted samples.
However, unlike neutrally buoyant particles, solid waste, soil, and smoke are mainly inorganic particles or mineral particles and have a relatively high density (usually 2 to 3 g/cm) 3 Even up to 6-7 g/cm 3 ) In a conventional microfluidic system, stable suspension and circulation are difficult to realize, and problems such as deposition, blockage and the like easily occur. For example, when a syringe pump is used for introducing a non-neutrally buoyant particle sample, the sample can be deposited in the syringe, so that the sample cannot be introduced, and when a peristaltic pump is used for pumping the non-neutrally buoyant particle, the flow pulse fluctuation is easy to occur, or when a matched soft buoyancy particle is usedAnd (4) depositing in the tube.
For non-neutrally buoyant particles, harding and Stokes have made theoretical inferences about their effect on gravity based on fluid mechanics (j. Fluidmech.,2020,902 a 4) and found: when the non-neutrally buoyant particle size is small, its effect in the vertical direction is negligible but affects the horizontal position of the particle, whereas when the non-neutrally buoyant particle size is large, the vertical effect cannot be ignored and is more difficult to describe by numerical simulation analysis.
However, the above studies are only illustrated by numerical analysis and theoretical derivation, and there are few practical successful cases of applying the microfluidic technology to the non-neutrally buoyant particles at home and abroad, and there is no direct evidence for the flow behavior of the non-neutrally buoyant particles in the vertical and horizontal directions of the microfluidic. The reason for this is that the whole microfluidic system is difficult to operate smoothly because the design and control of the sample input system for the non-neutrally buoyant particles are not performed at present.
In view of the above, it is necessary to provide a microfluidic device, a microfluidic sample input system and a control method thereof, so as to solve or at least alleviate the technical defects that the non-neutral buoyancy particles are not suitable for a microfluidic system, and sample deposition and flow pulse fluctuation are easily generated in a sample introduction process.
Disclosure of Invention
The invention mainly aims to provide a microfluidic device, a microfluidic sample input system and a control method, and aims to solve the problems that non-neutral buoyancy particles cannot be suitable for a microfluidic system and sample deposition and flow pulse fluctuation are easy to generate in the sample introduction process.
In order to achieve the above object, the present invention provides a microfluidic sample input system suitable for non-neutrally buoyant particles, comprising a sample storage assembly, a constant pressure air pump and a control end;
the sample storage assembly comprises a sample storage container and a suspension mechanism for applying suspension acting force to sample liquid in the sample storage container;
the air pressure input end of the constant pressure air pump is communicated with an external air bottle, the air pressure output end of the constant pressure air pump is communicated with the air inlet end of the sample storage container through a first air guide pipe, and the air inlet end of the sample storage container is higher than the liquid storage height of the sample storage container;
the sample storage container is communicated with the microfluidic device through a first liquid guide pipe, a liquid inlet end of the first liquid guide pipe extends into a liquid storage range of the sample storage container, a first flow sensor is arranged on the first liquid guide pipe, and the first flow sensor is in communication connection with the control end;
the control end is in communication connection with the constant-pressure air pump so as to control the flow of the sample liquid according to the information fed back by the first flow sensor.
Further, the microfluidic sample input system further comprises a water storage container;
the air pressure output end of the constant pressure air pump is communicated with the air inlet end of the water storage container through a second air conduit, and the air inlet end of the water storage container is higher than the liquid storage height of the water storage container;
the water storage container is communicated with the micro-fluidic device through a second liquid conduit, the liquid inlet end of the second liquid conduit extends into the liquid storage range of the water storage container, a second flow sensor is arranged on the second liquid conduit, and the second flow sensor is in communication connection with the control end.
Furthermore, the joint of the sample storage container and the first gas conduit, the joint of the sample storage container and the first liquid conduit, the joint of the water storage container and the second gas conduit, and the joint of the water storage container and the second liquid conduit are all hermetically arranged.
Further, the suspension mechanism comprises one or more of a stirring paddle, a magnetic stirrer and an ultrasonic disperser.
Further, the first liquid conduit has an inner diameter of less than 0.8mm.
The invention provides a microfluidic device suitable for non-neutrally buoyant particles, comprising a microfluidic device and a sample input system as described in any one of the above.
Further, the first liquid conduit in the sample input system is a polytetrafluoroethylene tube;
a sample introduction interface communicated with the first liquid conduit is formed in the micro-fluidic device, and the hydraulic diameter of a micro pipeline in the micro-fluidic device is less than 0.8mm; the micro-fluidic device is made of polydimethylsiloxane;
the inner diameter of the sample feeding interface is smaller than the outer diameter of the first liquid conduit.
The invention also provides a microfluidic sample input control method suitable for the non-neutrally buoyant particles, which is characterized in that the microfluidic sample input system is adopted to control microfluid to flow into a microfluidic device.
Further, the method comprises the following steps:
s1, controlling the suspension mechanism to be opened so as to enable a sample in the sample storage container to be in a suspension state;
s2, controlling the constant-pressure air pump to be started to enable the sample liquid in the sample storage container to flow into the microfluidic device;
and S3, controlling the air pressure output by the constant-pressure air pump according to the flow information fed back by the flow sensor so as to maintain the flow of the sample liquid in a stable state.
Further, the flow rate of the sample liquid is controlled to be 600-1500 muL/min in the process that the sample liquid flows into the microfluidic device.
Compared with the prior art, the invention has at least the following advantages:
the invention provides an external force suspension-constant pressure constant flow microfluidic sample input system and a control method suitable for non-neutral buoyancy particles, which ensure the suspension control, the sealing control, the flow path control, the flow control and the program control of the non-neutral buoyancy particles in a microfluidic system, so that the non-neutral buoyancy particles stably circulate in the microfluidic system at a controllable flow rate, the sedimentation, the blockage and the flow pulse generation of the non-neutral buoyancy solid waste particles in a container and a pipeline are avoided, and the system and the method have stronger applicability and universality compared with the traditional microfluidic control method and technology.
Specifically, the non-neutral buoyancy solid waste particles are suspended through external force, so that the non-neutral buoyancy solid waste particles are in a suspended state before entering the liquid guide pipe; the flow pulse fluctuation of the non-neutral buoyancy solid waste particles in the flowing process is avoided through the constant-pressure air pump, and the particles can be prevented from settling due to the combination of external force suspension and the constant-pressure air pump; through the design of the gas conduit and the liquid conduit, the connectivity and the air tightness among the constant-pressure air pump, the sample storage container and the liquid conduit are ensured, and a foundation is provided for the effective flow of sample liquid; by arranging the control end and the flow sensor, the flow control of the sample liquid in the flow process is ensured, and the particle deposition and flow pulse fluctuation caused by unstable flow are avoided; the flow velocity of the sample liquid is ensured by setting the pipe diameter of the liquid conduit and the pipe diameter inside the microfluidic device.
Drawings
In order to more clearly illustrate the embodiments or technical solutions of the present invention, the drawings used in the embodiments or technical solutions of the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the structures shown in the drawings without creative efforts.
Fig. 1 is a schematic block diagram of a microfluidic device according to example 1;
figure 2 is a microimage of the flow of non-neutrally buoyant particles and neutrally buoyant particles in a microfluidic device according to example 1.
Reference numerals are as follows: 1. a control end; 2. a constant pressure air pump; 3. a sample storage bottle; 4. a water storage bottle; 5. a first flow sensor; 6. a second flow sensor; 7. a microfluidic device; 8. and (4) collecting the container.
The implementation, functional features and advantages of the present invention will be further explained with reference to the accompanying drawings.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without inventive efforts based on the embodiments of the present invention, are within the scope of protection of the present invention.
Moreover, the technical solutions in the embodiments of the present invention may be combined with each other, but it is necessary to be based on the realization of the technical solutions by those skilled in the art, and when the technical solutions are contradictory to each other or cannot be realized, such a combination of the technical solutions should not be considered to exist, and is not within the protection scope claimed by the present invention.
When numerical ranges are given in the examples, it is understood that both endpoints of each of the numerical ranges and any value therebetween can be selected unless the invention otherwise indicated. 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 to which this invention belongs and the description of the present invention, and any methods, apparatuses, and materials similar or equivalent to those described in the examples of the present invention may be used to practice the present invention.
In order to prevent the non-neutral buoyancy particles from generating sedimentation and flow pulse fluctuation when entering the microfluidic device 7, so that the non-neutral buoyancy particles can be applicable to the microfluidic technology, the invention creatively provides a microfluidic sample input system applicable to the non-neutral buoyancy particles, which comprises a sample storage assembly, a constant pressure air pump 2 and a control end 1.
The sample storage assembly comprises a sample storage container and a suspension mechanism for applying suspension acting force to sample liquid in the sample storage container, the sample storage container is used for containing sample liquid containing non-neutrally buoyant particles, the particle density of the non-neutrally buoyant particles is larger than that of water, and the density of the non-neutrally buoyant particles is larger than that of water.
The air pressure input end of the constant pressure air pump 2 is communicated with an external air bottle, and the air pressure output end of the constant pressure air pump 2 is communicated with the air inlet end of the sample storage container through a first air conduit; the air inlet end of the sample storage container is higher than the liquid storage height of the sample storage container, so that the sample liquid is pushed to flow by air pressure.
The sample storage container is communicated with the microfluidic device 7 through a first liquid guide pipe, and the liquid inlet end of the first liquid guide pipe extends into the liquid storage range of the sample storage container so as to ensure that sample liquid can be pressed into the first liquid guide pipe under the action of air pressure; a first flow sensor 5 is arranged on the first liquid conduit, and the first flow sensor 5 is in communication connection with the control end 1.
The control end 1 is in communication connection with the constant pressure air pump 2 to control the flow of the sample liquid according to the information fed back by the first flow sensor 5. It should be noted that the control terminal 1 can process the received information and control the output of the air pressure in the constant pressure air pump 2.
In order to further adapt to the microfluidic technology, the microfluidic sample input system further comprises a water storage container, the configuration of the water storage container and the corresponding gas-liquid pipeline can be consistent with the sample storage container, and certainly, the water storage container does not need to be matched with a suspension mechanism because water is contained in the water storage container. Specifically, the method comprises the following steps:
the air pressure output end of the constant pressure air pump 2 is communicated with the air inlet end of the water storage container through a second air conduit, and the air inlet end of the water storage container is higher than the liquid storage height.
The water storage container is communicated with the microfluidic device 7 through a second liquid conduit, the liquid inlet end of the second liquid conduit extends into the liquid storage range of the water storage container, a second flow sensor 6 is arranged on the second liquid conduit, and the second flow sensor 6 is in communication connection with the control end 1.
The sample storage container and the water storage container can both adopt liquid storage bottles as corresponding containers, the second gas guide pipe and the first gas guide pipe can be made of the same material and have the same pipe diameter, and the connection modes of the second gas guide pipe and the first gas guide pipe with the constant-pressure air pump 2 and the microfluidic device 7 can also be the same; the second liquid conduit and the first liquid conduit can be of the same pipe diameter and the same material, and the connection mode of the second liquid conduit and the constant pressure air pump 2 and the microfluidic device 7 can also be the same.
The first flow sensor 5 and the second flow sensor 6 may be in the form of flow meters, that is, the first liquid conduit and the second liquid conduit may be two sections, and the two sections are communicated through the flow meters.
In order to ensure the leakproofness of admitting air and feed liquor in-process, avoid producing gas fluctuation and flow fluctuation, store up the appearance container with the junction of first gas pipe store up the appearance container with the junction of first liquid pipe water storage container with the junction of second gas pipe and water storage container with the equal airtight setting in junction of second liquid pipe, the position that the pipeline passed the container promptly needs airtightly to gas leakage prevention. In addition, when a flowmeter is used, each liquid conduit needs to be hermetically sealed even when connected to a flowmeter. It should be understood that the sealing arrangement is to seal the space between the outer wall of the pipeline and the inner wall of the container interface to ensure air tightness, and the sealing arrangement cannot be mistakenly understood as sealing the pipe orifice of the pipeline, and the pipe orifice cannot be sealed in the present invention.
As an illustration of the suspension mechanism, the suspension mechanism includes one or more of a paddle, a magnetic stirrer, and an ultrasonic disperser. For example: the sample in the sample storage bottle 3 can be dispersed by adopting an ultrasonic dispersion instrument, and then the sample storage bottle 3 is placed in a magnetic stirrer for continuous stirring, so that the sample is continuously in a suspension state in the sample introduction process.
In order to ensure a fast flow rate of the sample during sample introduction, the inner diameter of the first liquid conduit is less than 0.8mm.
The invention also provides a microfluidic device suitable for non-neutrally buoyant particles, comprising a microfluidic device 7 and further comprising a sample input system as described in any one of the above. Furthermore, a collection container 8 or an analysis subsystem may be included, if desired, said collection container 8 and analysis subsystem being adapted to receive via a conduit a liquid flowing out of said microfluidic device 7.
Wherein the first liquid conduit in the sample input system is a Polytetrafluoroethylene (PTFE) tube.
A sample introduction interface communicated with the first liquid conduit is formed in the micro-fluidic device 7, and the hydraulic diameter of a micro-pipeline in the micro-fluidic device 7 is less than 0.8mm; the material of the micro-fluidic device 7 is Polydimethylsiloxane (PDMS); the inner diameter of the sample feeding interface is smaller than the outer diameter of the first liquid conduit. In addition, the microfluidic device 7 may further include a water inlet port so as to be communicated with the second liquid conduit, and an inner diameter of the water inlet port is smaller than an outer diameter of the first liquid conduit.
The invention also provides a microfluidic sample input control method suitable for non-neutrally buoyant particles, which adopts the microfluidic sample input system as described in any one of the above to control microfluid to flow into the microfluidic device 7.
To be suitable for use with non-neutrally buoyant particles, the steps of the microfluidic sample input control method comprise:
s1, controlling the suspension mechanism to be opened so as to enable the sample in the sample storage container to be in a suspension state;
s2, controlling the constant-pressure air pump 2 to be started to enable the sample liquid in the sample storage container to flow into the microfluidic device 7;
and S3, controlling the air pressure output by the constant-pressure air pump 2 according to the flow information fed back by the flow sensor so as to maintain the flow of the sample liquid in a stable state.
Wherein, in the process that the sample liquid flows into the microfluidic device 7, the flow rate of the sample liquid is controlled to be 600-1500 muL/min.
For the understanding of those skilled in the art, the core idea of the present invention can be understood as follows:
1. suspension control: the non-neutral buoyancy solid waste particles are kept in a uniform suspension state in the liquid storage bottle through an external force;
2. and (3) sealing control: the sample storage container, the gas conduit, the liquid conduit and the microfluidic device 7 are ensured to be closed;
3. controlling a flow path: the sizes of the gas-liquid conduit and the microfluidic pipeline are set, so that the sample is ensured to flow in a suspension state all the time;
4. flow control: the flow in the closed system is ensured to be stable by the constant pressure air pump 2.
5. And (3) program control: and a flow sensor and a control end 1 are arranged, and the flow is fed back and determined according to the relevance between the flow and the air pressure.
In order to realize suspension control, the invention ensures that the non-neutral buoyancy solid waste particles are kept in a uniform suspension state in the sample storage container through external force, such as external force conditions of a stirring paddle, magnetic stirring or ultrasonic dispersion and the like, and ensures that a sample can be uniformly introduced into a microfluidic flow path and a microfluidic device 7. The invention can disperse the sample liquid by ultrasonic for 10 minutes, and then magnetically stir at 200-800 rpm, thereby ensuring that the non-neutral buoyancy solid waste particles are kept in a suspension state in the liquid storage bottle.
In order to realize the sealing control, the connection parts of the invention are hermetically arranged, specifically, a PU pipe is used for communicating a constant pressure air pump 2 and a liquid storage bottle, the constant pressure air pump 2 is connected with the PU pipe through a pneumatic connector, the connection parts of the liquid storage bottle and the PU pipe are hermetically connected through an airtight connector, and the airtight connector can be a threaded pagoda connector; the PTFE tube is used for communicating the liquid storage bottle and the flowmeter, and the flowmeter and the microfluidic device 7, the joint of the PTFE tube and the liquid storage bottle is hermetically connected through an airtight joint, the airtight joint can be an inverted cone joint, the joint of the PTFE tube and the flowmeter can also be connected through the inverted cone joint, the PTFE tube and the microfluidic device 7 can be directly inserted for communication, when the PTFE tube is connected with the microfluidic device 7, the PTFE tube can be directly inserted into the microfluidic device 7 which is perforated in advance (namely can be directly inserted into a sample inlet interface and a water inlet interface), the perforation diameter (1.4 mm) is smaller than the outer diameter (1.6 mm) of the PTFE tube, and the air tightness of the interface is ensured through the elasticity of PDMS materials of the microfluidic device 7; the liquid storage bottle can be a blue-mouth bottle, and the bottle cap is provided with two spiral airtight interfaces for connecting the gas conduit and the liquid conduit and matching with corresponding connectors when in connection.
In order to realize flow path control, the inner diameter of the first liquid conduit is less than 0.8mm, the first liquid conduit is made of PTFE plastic, and the first gas conduit is made of a PU (polyurethane) hard plastic pipe so as to be convenient for bearing pressure. The microfluidic device 7 is bonded by adopting Polydimethylsiloxane (PDMS) elastic materials on two sides through an ionic technology, and the hydraulic diameter of a micro-pipeline in the microfluidic device 7 is smaller than 0.8mm. Namely, the inner diameter of a connecting pipeline for connecting the liquid storage bottle, the flow sensor and the microfluidic device 7 is less than 0.8mm, the hydraulic diameter of a micro pipeline in the microfluidic device is less than 0.8mm, and the cross section of an inner cavity of the micro pipeline can be smaller than that of the first gas conduit.
In order to realize flow control, aiming at the pipeline data related to the invention, the flow of the non-neutral buoyancy particle sample liquid can be controlled to be 600-1500 muL/min, the flow of water is 600-1500 muL/min, and the total flow in the micro-fluidic device 7 is 1200-3000 muL/min. Wherein, the range of the Relo number Re of the pipeline of the microfluidic device 7 is controlled between 100 and 400.
In order to realize program control, flow data is transmitted to the control end 1 through the flow sensor, and the non-neutral buoyancy solid waste particle sample liquid is input to the microfluidic device 7 at a constant flow rate by adjusting the output air pressure of the constant pressure air pump 2 through the control end 1.
To facilitate a further understanding of the invention for those skilled in the art, reference will now be made to the following examples:
comparative example 1
Two non-neutral buoyancy particle sample liquids (a lead sulfate particle suspension and a jarosite particle suspension) are respectively introduced into the micro-fluidic device 7 by adopting a peristaltic pump, and the specific method conditions are as follows:
peristaltic pumps pump samples into the microfluidic system at 1000. Mu.L/min, 1200. Mu.L/min and 1400. Mu.L/min.
The peristaltic pump adopts 2mm external diameter 1mm internal diameter hose pump income sample liquid, and the hose passes through the pipeline adapter and connects the Tygon hose of 0.51mm internal diameter, then connects to micro-fluidic device 7 through the Tygon hose.
The non-neutral buoyancy particle sample liquid is subjected to ultrasonic dispersion for 10min in advance, is kept in a uniform suspension state through magnetic stirring, and is pumped into the microfluidic device 7 through a peristaltic pump.
Finally, under different flow rates, the non-neutral buoyancy particles are introduced into the microfluidic system through the peristaltic pump, a large amount of particle sedimentation is found in a hose matched with the peristaltic pump for the non-neutral buoyancy particles (lead sulfate) with large density and particle size, and for the non-neutral buoyancy particles (sodium jarosite) with small density and particle size, part of particle liquid is introduced into the microfluidic device 7, so that a sample cannot be uniformly introduced into the microfluidic device 7; the flow conditions in the microfluidic device 7 were observed by a microscope, indicating that the peristaltic pump had significant flow pulses and that stable flow of the microfluid in the microfluidic device 7 could not be ensured.
Comparative example 2
Two non-neutral buoyancy particle sample liquids (a lead sulfate particle suspension and an jarosite particle suspension) are introduced into the microfluidic device 7 by using a syringe pump. The specific method conditions are as follows:
the syringe pumps pumped the sample into the microfluidic system at 1000. Mu.L/min, 1200. Mu.L/min and 1400. Mu.L/min.
The syringe is selected to be 50mL screw specification, is connected with a Tygon hose with the inner diameter of 0.51mm through a flat injection needle with the outer diameter of 0.6mm, and is further connected to the microfluidic device 7.
The non-neutrally buoyant particle sample liquid is ultrasonically dispersed for 10min in advance and is sucked into a syringe for use.
The final conclusion is that during the process of introducing the non-neutrally buoyant particles into the microfluidic system by the syringe pump, both of the non-neutrally buoyant particles settle in the syringe at different flow rates, and the non-neutrally buoyant particles in the sample fluid cannot be introduced into the microfluidic device 7.
Example 1
This example is based on five parts of sample suspension control, sample sealing control, flow path control, flow rate control and program control.
Referring to fig. 1, the microfluidic device of this embodiment is provided with a microfluidic sample input system and microfluidic means 7, and in addition, a collection container 8. Wherein, microfluid sample input system includes constant pressure air pump 2, storage bottle 3 (storage appearance container), water storage bottle 4 (water storage container) and control end 1.
The specific component relationship and gas-liquid path connection mode of the embodiment are as follows: the air pressure input end of the constant pressure air pump 2 is connected with an air bottle through a PU hard plastic pipe with 8mm external diameter and 6mm internal diameter, thereby providing air pressure; the air pressure output end is respectively connected with the sample storage bottle 3 and the water storage bottle 4 through a PU air pipe with the outer diameter of 4mm and the inner diameter of 2mm, and the air tightness is required to be ensured at each interface part connected with the air passage.
The sample storage bottle 3 and the water storage bottle 4 are respectively connected to an inlet of the microfluidic device 7 through PTFE plastic liquid guide pipes with the outer diameter of 1.5mm and the inner diameter of 0.6mm, and when the sample storage bottle 3 and the water storage bottle 4 are connected, the liquid inlet ends of the PTFE plastic liquid guide pipes need to be ensured to be deep below the liquid level, so that sample liquid or water can be pressed into the pipes under pressure.
Flow sensors are connected between the sample storage bottle 3, the water storage bottle 4 and the microfluidic device 7 through PTFE plastic liquid guide pipes, and the flow sensors are divided into a first flow sensor 5 for detecting the flow of sample liquid and a second flow sensor 6 for detecting the flow of water; the outlet section of the microfluidic device 7 is connected to a collection vessel by a tygon tube.
In addition, the constant-pressure air pump 2 is connected with the computer end (control end 1) through a data line to control the air pressure output, and the flow sensor is connected with the computer end (control end 1) through the data line to feed back flow data, so that air pressure-flow feedback is formed, and the constant flow of the sample liquid is input into the microfluidic system.
This example also used a lead sulfate particle suspension and an astrakanite particle suspension to test the above structure and a polystyrene particle suspension for comparison.
Since the density of the lead sulfate particles is 6.2kg/m 3 The density of the jarosite particles is 3.2kg/m 3 The two particles are non-neutral buoyancy particles, and the particles of the particle suspension liquid of the two particles are easy to precipitate under the condition of not carrying out ultrasonic dispersion and magnetic stirring, so that the sample particles cannot be introduced into a microfluidic system or a blocking conduit.
The non-neutral buoyancy particles are dispersed for 10min by ultrasonic in advance and then kept in a suspension state by magnetic stirring. The non-neutral buoyancy solid waste particle liquid storage bottle needs to be stirred by external force to keep the particle suspension state, and is introduced into the microfluidic device 7 in a suspension liquid state. Secondly, high flow rates in the micro-scale conduits and microchannels of the microfluidic device 7 may ensure particle suspension.
Under the condition that the normal operation of a gas-liquid flow path is ensured, the non-neutral buoyancy solid waste particles are kept in a suspension state in the liquid storage bottle, the constant air pressure output of the constant pressure air pump 2 is controlled by a computer end program to realize the specific flow condition of constant flow, the sample particle liquid is input into a microfluidic system and the microfluidic function is realized, the stable flow is kept, and the flow pulse phenomenon does not occur.
Referring to FIG. 2, by the external force suspension-constant pressure constant flow microfluid control method of the non-neutral solid waste particles of the present invention, the lead sulfate and jarosite particles, which are non-neutral buoyancy particles with a concentration of 40g/L, are introduced into the microfluidic device 7 at a flow rate of 1000. Mu.L/min, 1200. Mu.L/min and 1400. Mu.L/min, respectively, and the polystyrene particles (neutral buoyancy particles, particle density of 1.1 kg/m) 3 ) Also into the microfluidic device 7 under identical conditions.
It should be noted that since water also has a flow rate equivalent to that of the sample liquid, the flow rates shown in fig. 2 are the total flow rate in the microfluidic device 7, i.e., 2000 μ L/min in the figure corresponds to a sample liquid flow rate of 1000 μ L/min, 2400 μ L/min corresponds to a sample liquid flow rate of 1200 μ L/min, and 2800 μ L/min corresponds to a sample liquid flow rate of 1400 μ L/min.
The micro-channel in the micro-fluidic device 7 is observed through a microscope, and the fact that the lead sulfate particles and the jarosite particles are successfully introduced into the micro-fluidic device 7 at a constant flow rate is found, and in the micro-channel, obvious inertial flow behaviors occur at different flow rates, and the behaviors are similar to those of polystyrene particles.
In the above technical solutions, the above are only preferred embodiments of the present invention, and the technical scope of the present invention is not limited thereby, and all the technical concepts of the present invention include the claims of the present invention, which are directly or indirectly applied to other related technical fields by using the equivalent structural changes made in the content of the description and the drawings of the present invention.

Claims (5)

1. A microfluidic sample input control method suitable for non-neutrally buoyant particles is characterized in that a microfluidic sample input system is adopted to control microfluid to flow into a microfluidic device, the microfluid contains the non-neutrally buoyant particles, and the particle density of the non-neutrally buoyant particles is higher than that of water;
the microfluidic sample input system comprises a sample storage assembly, a constant-pressure air pump and a control end;
the sample storage assembly comprises a sample storage container and a suspension mechanism for applying suspension acting force to sample liquid in the sample storage container;
the air pressure input end of the constant pressure air pump is communicated with an external air bottle, the air pressure output end of the constant pressure air pump is communicated with the air inlet end of the sample storage container through a first air guide pipe, and the air inlet end of the sample storage container is higher than the liquid storage height of the sample storage container;
the sample storage container is communicated with the microfluidic device through a first liquid guide pipe, the inner diameter of the first liquid guide pipe is smaller than 0.8mm, the liquid inlet end of the first liquid guide pipe extends into the liquid storage range of the sample storage container, a first flow sensor is arranged on the first liquid guide pipe, and the first flow sensor is in communication connection with the control end;
the control end is in communication connection with the constant-pressure air pump so as to control the flow of the sample liquid according to the information fed back by the first flow sensor;
the microfluidic sample input control method comprises the following steps:
s1, controlling the suspension mechanism to be opened so as to enable the sample in the sample storage container to be in a suspension state;
s2, controlling the constant-pressure air pump to be started to enable the sample liquid in the sample storage container to flow into the microfluidic device;
s3, controlling the air pressure output by the constant-pressure air pump according to flow information fed back by the flow sensor so as to maintain the flow of the sample liquid in a stable state; and controlling the flow rate of the sample liquid to be 600-1500 mu L/min in the process of flowing the sample liquid into the microfluidic device.
2. The microfluidic sample input control method for non-neutrally buoyant particles of claim 1 wherein the microfluidic sample input system further comprises a water reservoir;
the air pressure output end of the constant pressure air pump is communicated with the air inlet end of the water storage container through a second air conduit, and the air inlet end of the water storage container is higher than the liquid storage height of the water storage container;
the water storage container is communicated with the micro-fluidic device through a second liquid conduit, the liquid inlet end of the second liquid conduit extends into the liquid storage range of the water storage container, a second flow sensor is arranged on the second liquid conduit, and the second flow sensor is in communication connection with the control end.
3. The microfluidic sample input control method suitable for the non-neutrally buoyant particles according to claim 2, wherein a joint of the sample storage container and the first gas conduit, a joint of the sample storage container and the first liquid conduit, a joint of the water storage container and the second gas conduit, and a joint of the water storage container and the second liquid conduit are hermetically arranged.
4. The microfluidic sample input control method for non-neutrally buoyant particles according to claim 1 wherein the suspension mechanism comprises one or more of a paddle, a magnetic stirrer, and an ultrasonic disperser.
5. The microfluidic sample input control method for non-neutrally buoyant particles of claim 1 wherein the first liquid conduit in the sample input system is a polytetrafluoroethylene tube; a sample introduction interface communicated with the first liquid conduit is formed in the micro-fluidic device, and the hydraulic diameter of a micro pipeline in the micro-fluidic device is less than 0.8mm; the micro-fluidic device is made of polydimethylsiloxane;
the inner diameter of the sample feeding interface is smaller than the outer diameter of the first liquid conduit.
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