CN110918139B - Microfluidic chip, device containing microfluidic chip and sample concentration method - Google Patents
Microfluidic chip, device containing microfluidic chip and sample concentration method Download PDFInfo
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- CN110918139B CN110918139B CN201811098975.7A CN201811098975A CN110918139B CN 110918139 B CN110918139 B CN 110918139B CN 201811098975 A CN201811098975 A CN 201811098975A CN 110918139 B CN110918139 B CN 110918139B
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
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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
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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
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
- B01L2400/0418—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic electro-osmotic flow [EOF]
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N2001/4038—Concentrating samples electric methods, e.g. electromigration, electrophoresis, ionisation
Abstract
The invention relates to the field of microfluidics, in particular to a microfluidic chip, a device containing the microfluidic chip and a sample concentration method. The invention uses alternating current seepage and positive dielectrophoresis force to concentrate the relative areas of liquid drops in a continuous fluid (continuous flow) state, and then cuts redundant liquid drops through an acute angle between outlets to obtain concentrated sample liquid drops. Concentrated droplet samples have wide ranging applications, and can be analyzed and cultured after drug sensitive assays or small sample numbers can be concentrated if the sample is cell/bacteria. If the sample is DNA, the high concentration in the liquid drop after concentration can effectively promote the subsequent amplification, analyze or save the hybridization efficiency, and increase the collision probability due to the increase of the sample concentration in the liquid drop, thus shortening the reaction time.
Description
Technical Field
The invention relates to the field of microfluidics, in particular to a microfluidic chip, a device containing the microfluidic chip and a sample concentration method.
Background
Microfluidic chip technology (Microfluidics), also known as Lab-on-a-chip, is capable of integrating the basic functions of conventional biological and chemical laboratories, including sample separation, preparation, chemical reactions, detection, etc., on a few square centimeters of microchip.
The microfluidic chip has the characteristics of controllable liquid flow, extremely small consumption of samples and reagents, ten times or hundreds times higher analysis speed and the like, can simultaneously analyze hundreds of samples in a few minutes or even shorter, and can realize the whole pretreatment and analysis processes of the samples on line.
Droplet microfluidic technology is an important branch of microfluidic chip technology. Droplet microfluidic technology was developed in traditional single-phase microfluidic chip technology, and was first taught by Rustem f. Ismagilov, university of chicago, to first propose a three-inlet T-type microfluidic chip design, and to gain widespread attention and use in the next few years. Compared with a single-phase microfluidic system, the water/oil two-phase separation system has the advantages of less consumption of samples and reagents, higher mixing speed, difficult cross contamination, easy control and the like due to the characteristic of water/oil two-phase separation. Therefore, the method has important application in the fields of rapid high-flux detection of pollutants, separation and cultivation of biological samples, observation of chemical reaction progress and the like. The micro-droplet has the advantages of high flux, no cross contamination and the like, and has great application potential in the fields of ink-jet printing, micro-mixing, DNA analysis, material synthesis, protein crystallization and the like.
For early diagnosis purposes, the concentration of the analyte in the sample is usually very small, and the trace sample (e.g., DNA, cells, bacteria, biological proteins) usually presents considerable challenges for testing, so that concentration of the sample is particularly important.
Electroosmotic flow driving technology is one of the important components of microfluidic chips. The electroosmotic flow micropump has the advantages of easy processing and control, no need of moving parts, high repeatability and reliability and the like. At present, electroosmosis flow is generally divided into two modes, namely direct current electroosmosis and alternating current electroosmosis. Dc electroosmosis requires applying voltages of hundreds or even thousands of volts to the micro-channels, which can cause electrochemical reactions between the electrodes and the solution, generating bubbles, joule heating effects, etc., all of which limit the development of dc electroosmosis micropumps.
Disclosure of Invention
In view of the above, the present invention provides a microfluidic chip, an apparatus including the microfluidic chip, and a method for concentrating a sample. The present invention aims to concentrate a sample and remove excess liquid, and uses a microfluidic chip-mounting electrode to concentrate the sample.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a microfluidic chip, which comprises a substrate, wherein the substrate is provided with a sample inlet 1, an outlet 2 and a micro-channel 3 arranged between the sample inlet 1 and the outlet 2;
the substrate is further provided with electrodes 4, and the electrodes 4 apply alternating current seepage disturbing forces and/or dielectrophoresis forces to the micro-fluidic channels 3.
In some embodiments of the invention, the electrode 4 is an asymmetric alternating current electrode.
In some embodiments of the present invention, the electrode 4 is a three-stage asymmetric electrode, the electrode 4 including a middle electrode and two side electrodes, the middle electrode having a width greater than the width of the two side electrodes.
In some embodiments of the invention, the width of the middle electrode is at least 2 times the width of the two side electrodes.
In some embodiments of the invention, the width of the intermediate electrode is at least the width of the two-sided electrodeMultiple times.
In some embodiments of the invention, the two electrodes are applied with voltages in phase and the middle electrode is applied with voltages in opposite phase to the two electrodes.
In some embodiments of the invention, the frequency of the electrode 4 is: a flow field capable of generating alternating current seepage; and capable of generating a positive dielectrophoresis force; and the disturbing force of alternating current seepage is larger than the positive dielectrophoresis force, so as to effectively control particles (d) with diameters below 2 microns<2 m)。
In some embodiments of the invention, the frequency of the electrode 4 is 1/2 pi R m C D The method comprises the steps of carrying out a first treatment on the surface of the Wherein R is m For the resistance of the solution in the sample, C D Is an electric double layer capacitor.
In some embodiments of the invention, the number of outlets 2 is at least 2, and the angle between 2 adjacent outlets 2 is less than 60 ° (an angle of 30 ° is preferred in the examples of the invention).
In other embodiments of the invention, the electrode 4 is a continuously skewed alternating current electrode; the frequency of the continuously skewed AC electrode is capable of generating a negative dielectrophoresis force effective to manipulate particles (d) having a diameter of 0.5 microns or more>0.5 m)。
On the basis, the invention also provides a device for concentrating the sample, which comprises the microfluidic chip.
The invention also provides an application of the microfluidic chip or the device in concentrating samples; the sample comprises a mixture of one or more of nucleic acids, cells, bacteria or proteins.
The invention also provides a method for concentrating samples based on the microfluidic chip or the device, which comprises the following steps:
step 1: obtaining a sample based on a water-in-oil (water-in-oil) emulsion droplet state;
step 2: introducing the sample in the liquid drop state to the sample inlet 1;
step 3: and the frequency of the electrode 4 is regulated to generate alternating current seepage disturbing force and/or dielectrophoresis force to concentrate the sample in the liquid drop state, and the sample is cut and collected through an acute angle between the outlets 2 so as to reduce the liquid quantity of the product liquid drop and achieve the effect of improving the concentration of the sample to be tested in the liquid drop.
The beneficial effects of the invention include, but are not limited to:
A. alternating current percolation is a method that does not affect the sample and is widely used for manipulating, concentrating, transporting samples (DNA, cells, bacteria, biological proteins, etc.). Since alternating current seepage is the first disturbance of the fluid to drive the sample by the fluid, it can be said that the sample is kept in its original state.
B. The invention uses alternating current seepage and positive dielectrophoresis force to concentrate the relative areas of liquid drops in a continuous fluid (continuous flow) state, and then cuts redundant liquid drops through an acute angle between outlets to obtain concentrated sample liquid drops.
C. Concentrated droplet samples have wide ranging applications, and can be analyzed and cultured after drug sensitive assays or small sample numbers can be concentrated if the sample is cell/bacteria. If the sample is DNA, the high concentration in the liquid drop after concentration can effectively promote the subsequent amplification, analyze or save the efficiency of hybridization (hybridization), increase the collision probability due to the increase of the concentration of the sample in the liquid drop, and shorten the reaction time.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.
Fig. 1 is a schematic diagram of the working principle of a microfluidic chip provided by the invention; fig. 1 includes (a), (b), and (c); wherein (a) shows a schematic diagram of a disturbance force of alternating current seepage and a positive dielectrophoresis force; (b) When the sample is DNA or protein, the blue curve is the disturbance force of alternating current seepage, the green curve is the positive dielectrophoresis force applied to the sample, and when the sample is concentrated, the frequency of the disturbance force of alternating current seepage is selected to be larger than the positive dielectrophoresis force; (c) When the sample is bacteria, the blue curve is the disturbing force of alternating current seepage, the purple curve is the positive dielectrophoresis force applied to the sample, and when the sample is concentrated, the frequency of the disturbing force of alternating current seepage is selected to be larger than the frequency of the positive dielectrophoresis force;
fig. 2 shows a schematic structural diagram of a microfluidic chip provided by the present invention; fig. 2 includes a and B; wherein A shows a top view; b is a schematic view of the electrode 4 shown in the cross section of the tube (green dotted line direction); the chip structure and design are suitable for particles smaller than 2 microns, such as nucleic acid molecules, proteins, bacteria and the like;
FIG. 3 is a schematic diagram showing the structure of another micro-fluidic chip for concentrating cells/bacteria by pure negative dielectrophoresis provided by the invention; the chip structure and design are suitable for particles with the size larger than 0.5 micron and obvious dielectrophoresis force, such as bacteria, cells and the like;
wherein, 1-sample inlet; 2-outlet; 3-a microchannel; 4-electrode.
Detailed Description
The invention discloses a microfluidic chip, a device containing the microfluidic chip and a sample concentration method, and the technical parameters can be properly improved by a person skilled in the art by referring to the content of the text. It is expressly noted that all such similar substitutions and modifications will be apparent to those skilled in the art, and are deemed to be included in the present invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those skilled in the relevant art that variations and modifications can be made in the methods and applications described herein, and in the practice and application of the techniques of this invention, without departing from the spirit or scope of the invention.
The microfluidic chip, the device containing the microfluidic chip and the method for concentrating the sample provided by the invention can be purchased from the market.
The invention is further illustrated by the following examples:
the invention provides a microfluidic chip, which comprises a substrate, wherein the substrate is provided with a sample inlet 1, a sample outlet 2 and a micro-channel 3 arranged between the sample inlet 1 and the sample outlet 2; the substrate is further provided with electrodes 4, the electrodes 4 applying alternating current osmotic flow disturbing forces and/or dielectrophoresis forces to the micro-fluidic channels 3.
ACEO flow (AC elecroosmosis flow) principle: the cause of alternating current (AC Electro-Osmosis, ACEO) is attributable to the electric field parallel to the planar electrodesThe interaction of the component with charged ions adjacent to the electrode surface, the coulombic force (Columbic forces) caused by the charge of the electric double layer (electric double layer) (thickness 1-100 nm) of the electrode surface. The electroosmotic flow rate can be expressed by the Smoluchowski equation: u= -epsilonE/eta, where epsilon is the dielectric constant of the fluid, eta is the viscosity,/is->The potential of the surface potential, E is the strength of the applied electric field. In the state of non-uniform surface charges (such as asymmetric electrodes), the frequency of the alternating electric field can be controlled at a proper charge-discharge time constant by the alternating electric field, so that the charges in the electric double layer are no longer in poisson-boltzmann equilibrium, and polarization phenomenon (polarization) is generated. As a result, the applied electric field can penetrate the electric double layer to generate transient current, so that the electric double layer in a charged/discharged state is just like a capacitor. Since a large amount of charges (field-induced charges) induced on the electrode surface always remain in the same direction as the alternating electric field during the period in which the alternating electric field continuously changes direction, the change in the integrated and average charge density pulls the flow field disturbance, so-called alternating current percolation (ACEO), can exhibit a net flow of fluid. And the electric field frequency omega plays a key role in controlling ac current leakage. If ω is too high, the electric double layer cannot form significant charge polarization exchange to cause flow due to too short charge-discharge time of the electric field to the electric double layer. However, if ω is too low, the electric double layer has a strong shielding (screening) effect on the external electric field, causing the charge/discharge characteristic time of the circuit acting in the tangential direction of the charges in the current layer and the resistance: τ=r m C D Frequency f=1/2 pi R m C D Wherein R is m Resistance of solution, C D Is an electric double layer capacitor: c (C) D ~ε/λ。
According to the asymmetric electrode structure provided by the invention, residual (positive) chord voltage driving signals are applied to a group of large and small electrodes, and counter ion charges in an electric double layer are moved by coulomb force under the action of a tangential electric field to form electroosmotic flow.
The principle of the electric double layer capacitor is as follows: a voltage is applied to the upstanding electrode in contact with the electrolyte and ions of opposite charge accumulate at the electrode surface, an arrangement of charge carriers known as an electric double layer.
Under the action of AC electric field, polarized dielectric particles generate dielectrophoresis motion under the action of dipole moment. The magnitude of dielectrophoresis force and velocity can be determined according to the theory of electromagnetic field polarization.
After the alternating current electric field is introduced into the microfluidic chip, the fluid can generate internal flow under the action of the alternating current electric field, and the internal flow is represented as local vortex in the flow field or directional net flow of the fluid. Dielectrophoresis (DEP) technology is an important means of manipulating micro-nano scale dielectric particles with which different kinds of particles suspended in a fluid medium can be manipulated and identified. The flow of the microfluid under the external electric field is influenced by the conductivity of the fluid, the electrode structure, the external electric field, an external light source or a heat source and other factors; the magnitude and direction of the micro-nano particle dielectrophoresis force are influenced by a plurality of factors such as dielectric constant and conductivity of the fluid medium and the particles, particle radius, electric field distribution voltage amplitude and frequency. Under the same conditions, as the distance between the particles and the electrode increases, the dielectrophoresis force decays exponentially, only the dielectric particles in the region near the electrode exhibit a significant dielectrophoresis effect, and the phenomenon of particle dielectrophoresis on a submicron or nanometer scale is weaker.
Submicron and nanoscale particles, or particles outside the effective range of dielectrophoresis, sometimes also exhibit significant dielectrophoresis effects at weaker electric field strengths. This indicates that the dielectrophoresis effect and the action range of the micro-nano particles are interfered by the flow field where the micro-nano particles are positioned. Particles farther from the electrode are transported to the vicinity of the electrode due to the presence of eddies within the fluid, and are subjected to dielectrophoresis forces. The invention takes three-level asymmetric alternating current electrode pair micro-nano particle dielectrophoresis as an example, and can provide theoretical reference for efficient enrichment and control of micro-nano particles such as cells, proteins, nucleic acids and the like.
In some embodiments of the inventionThe electrode 4 is an asymmetric alternating current electrode. Preferably, the asymmetric electrode is a three-stage asymmetric electrode, comprising a middle electrode and two side electrodes, wherein the width of the middle electrode is larger than that of the two side electrodes. Preferably, the width of the middle electrode is at least 2 times the width of the two side electrodes. More preferably, the width of the intermediate electrode is at least the width of the two side electrodesMultiple times. Preferably, the two electrodes are applied with voltages in phase, and the intermediate electrode is applied with voltages in opposite phase to the two electrodes.
In some embodiments of the invention, the frequency of the electrode 4 is: a flow field capable of generating alternating current seepage; and capable of generating a positive dielectrophoresis force; and the disturbing force of alternating current seepage is larger than the positive dielectrophoresis force. Preferably, the frequency of the electrode 4 is 1/2 pi R m C D The method comprises the steps of carrying out a first treatment on the surface of the Wherein R is m For the resistance of the solution in the sample, C D Is an electric double layer capacitor.
The invention mainly provides a three-stage asymmetric electrode, wherein the width of a central wide electrode is required to be designed to be more than 2 times of the width of two thinner electrodes, so that vortex disturbance effect generated by alternating current seepage can concentrate net flow to a central large electrode due to the fact that vortex generated by the central wide electrode is larger than that of two thinner electrodes, and finally particles to be detected (such as DNA, protein, bacteria and the like) in liquid drops are concentrated at a fluid stagnation point in the center of the wide electrode, as shown in fig. 1 (a). While the strength of acto is related to RC time, i.e. frequency dependent (f=1/2 pi R m C D ) As before, excessively higher than 1/2 pi R m C D The frequency of (2) is too short, and the electric field can not form obvious charge polarization exchange to cause flow, so that ACEO effect is quite weak with flow field, and is too lower than 1/2 pi R m C D The frequency flow field of the electric double layer has stronger shielding effect on the external electric field, so that Maxwell force acting on the tangential direction of charges in the electric double layer is weakened or insufficient to drive fluid. ACEO is therefore only applied at a frequency in the range of 1/2 pi R m C D Is significantly higher in the vicinity of the frequency range of (2)The effect of the fast flow field is optimal because the dielectrophoresis effect exists when the alternating current electric field is applied, if the mechanism caused by the frequency exists in the positive dielectrophoresis force, the adsorption force can be provided to make the target particles/molecules attracted and concentrated towards the surface of the electrode, if the ACEO function is matched, the speed of the ACEO for bringing the target particles into the surface of the central electrode can be improved, and after the ACEO enters the central fluid stagnation point of the surface of the central wide electrode, the target particles/molecules can be maintained in the center by the positive dielectrophoresis force and are not easily brought out by the flow field, so the frequency condition of the electric field in which the optimal particles/molecules are concentrated in the center of the liquid drop is as follows:
1. the ACEO flow field is obviously induced by alternating current; and is also provided with
2. Simultaneously generating positive dielectrophoresis force; and is also provided with
3. ACEO flow field forces are greater than positive dielectrophoresis forces as shown in FIG. 1 (b, c).
In some embodiments of the invention, the number of outlets 2 is at least 2, and the angle between 2 adjacent outlets 2 is < 60 °.
In other embodiments of the invention, electrode 4 is a continuously skewed alternating current electrode; the frequency of the continuously skewed ac electrode can create a negative dielectrophoretic force.
On the basis, the invention also provides a device for concentrating the sample, which comprises the microfluidic chip provided by the invention.
The invention also provides application of the microfluidic chip or the device in concentrating samples; the sample comprises a mixture of one or more of nucleic acids, cells, bacteria or proteins. Any sample that can be separated based on the working principle of the present invention is within the protection scope of the present invention, and the present invention is not described herein.
The invention also provides a method for concentrating samples based on the microfluidic chip or the device, which comprises the following steps:
step 1: obtaining a sample of the emulsified liquid drop state;
step 2: introducing a sample in a liquid drop state to the sample inlet 1;
step 3: the frequency of the electrode 4 is regulated, alternating current seepage disturbing force and/or dielectrophoresis force is generated to concentrate the sample in the liquid drop state, the sample after concentration can be collected by cutting the sample at an acute angle between the outlets 2 and removing redundant liquid in the liquid drop.
The working principle of the microfluidic chip provided by the invention is as follows: the microfluidic chip provided by the present invention is as shown in fig. 2, for example, a concentrated DNA solution is used as a sample, the sample is first converted into an emulsified droplet state, then the emulsified droplet is injected into the chip, the droplet is filled in a pipeline, then the droplet is subjected to alternating current (AC Electro-Osmosis) interference force and dielectrophoresis force (dielectrophoresis) generated by an asymmetric electrode, a target object (for example, DNA but may also be cells, bacteria, etc.) in the droplet is brought to a stagnation area of a central electrode in the pipeline, the stagnation area is limited by the counter balance between the Alternating Current (AC) interference force and the dielectrophoresis, in an ideal state, all samples are concentrated in a middle area of the central electrode, finally the droplet is cut by an acute angle of an outlet structure when the droplet is moved to an outlet, the concentrated sample is collected by removing redundant liquid in the droplet, and by using the design, the detection target object (DNA, RNA, protein, bacteria, cells, etc.) in the droplet can be effectively concentrated, and the volume can be matched with a subsequent biochemical reaction experiment, and the required amount of the added reagent is synchronously reduced.
The design of the asymmetric electrode (fig. 2B) is based on the basic structure of alternating current seepage, the basic form is that a circulating flow field disturbance solution is generated when the symmetric electrode operates, the electrode is designed to be asymmetric based on the phenomenon, and the fluid phenomenon can generate a stagnation area on the electrode after antagonism due to the different magnitudes of flow field disturbance forces generated by the asymmetric electrode and positive dielectrophoresis attractive force generated by particles induced on the surface of the electrode. If the flow field turbulence force is smaller than the particle positive dielectrophoresis attraction force, the object is brought to the central electrode by the weak flow field turbulence force, but the strong positive dielectrophoresis force can pull the particles away from the central area of the electrode and adsorb the particles on the edge of the electrode (the edge of the electrode is a strong electric field region), the invention achieves the aim of concentration through the region.
In other embodiments, as shown in fig. 3, the negative dielectrophoresis repulsive force generated by the continuous deflection electrodes is used to concentrate particles in the center of the pipeline, redundant liquid is removed by the outlet structure, the size of the concentrated area is positively correlated with the distance between the deflection electrodes, the concentrated area with large (small) distance between the deflection electrodes is large (small), the dielectrophoresis force only acts on the strong electric field region, and the electric field decays exponentially, so that the influence range is only around the electrodes. However, the method can only affect the particle sample (d >500 nm) with a size larger than 500 nm, and has insufficient acting force on small molecular samples, such as weak dielectrophoresis force due to the nano-scale volume of biological protein and DNA, so that the sample cannot be effectively controlled, and thus the sample cannot be concentrated.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (4)
1. The microfluidic chip is characterized by comprising a substrate, wherein the substrate is provided with a sample inlet (1), an outlet (2) and a micro-channel (3) arranged between the sample inlet (1) and the outlet (2);
the substrate is also provided with an electrode (4), and the electrode (4) applies alternating current seepage disturbing force and dielectrophoresis force to the micro-channel (3);
the electrode (4) is an asymmetric alternating current electrode;
the electrodes (4) are three-stage asymmetric electrodes and continuous deflection alternating current electrodes, the three-stage asymmetric electrodes comprise middle electrodes and two side electrodes, and the width of the middle electrodes is larger than that of the two side electrodes;
the width of the middle electrode is at least 2 times of the width of the two side electrodes;
the frequency of the continuously skewed alternating current electrode is capable of generating a negative dielectrophoresis force;
the frequency of the three-stage asymmetric electrode is as follows: a flow field capable of generating alternating current seepage; and capable of generating a positive dielectrophoresis force; the disturbing force of alternating current seepage is larger than the positive dielectrophoresis force;
the frequency of the three-stage type asymmetric electrode is 1/2 pi R m C D The method comprises the steps of carrying out a first treatment on the surface of the Wherein R is m For the resistance of the solution in the sample, C D Is an electric double-layer capacitor;
the number of outlets (2) is at least 2, and the included angle between 2 adjacent outlets (2) is less than 60 degrees.
2. A device for concentrating a sample, comprising the microfluidic chip of claim 1.
3. Use of a microfluidic chip according to claim 1 or a device according to claim 2 for concentrating a sample; the sample comprises a mixture of one or more of nucleic acids, cells, bacteria or proteins.
4. A method of concentrating a sample based on the microfluidic chip of claim 1 or the device of claim 2, comprising the steps of:
step 1: obtaining a sample of the droplet state;
step 2: introducing the sample in the liquid drop state into the sample inlet (1);
step 3: and adjusting the frequency of the electrode (4), generating alternating current seepage disturbing force and dielectrophoresis force to concentrate the sample in the liquid drop state, and collecting the sample through acute angle cutting between the outlets (2).
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| CN111912697B (en) * | 2020-08-14 | 2023-03-07 | 南京原码科技合伙企业(有限合伙) | Rapid concentration device and method for pathogenic microorganisms |
| CN112226360A (en) * | 2020-08-14 | 2021-01-15 | 南京原码科技合伙企业(有限合伙) | System and method for automatically detecting pathogens in breath |
| CN113801964A (en) * | 2021-10-13 | 2021-12-17 | 四川大学 | Probe-free detection method of virus RNA |
| GB2618841A (en) * | 2022-05-20 | 2023-11-22 | Kromek Ltd | Processing module and method |
| CN117405757A (en) * | 2022-07-07 | 2024-01-16 | 珠海捷壹生物科技有限公司 | Apparatus for controlling charged particles in fluid and method for controlling movement of charged particles |
| CN117405758A (en) * | 2022-07-07 | 2024-01-16 | 珠海捷壹生物科技有限公司 | Microfluidic system for controlling charged particle movement and control method |
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