CN110918139A - Microfluidic chip, device containing same and sample concentration method - Google Patents
Microfluidic chip, device containing same and sample concentration method Download PDFInfo
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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. According to the invention, under the continuous fluid (continuous flow) state, the relative area concentration of liquid drops is carried out by using alternating current seepage flow and positive dielectrophoresis force, and then the cutting of redundant liquid drops is carried out through an acute angle between outlets, so as to obtain concentrated sample liquid drops. Concentrated droplet samples have a wide range of applications, and may be subjected to drug sensitive assays assuming the sample is a cell/bacterium or to analysis and culture after a small number of samples have been concentrated. If the sample is DNA, the subsequent amplification, analysis or hybridization efficiency can be effectively improved due to the high concentration in the liquid drop after concentration, and the reaction time can be shortened due to the increased collision probability caused by the increased sample concentration in the liquid drop.
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 microchip.
The micro-fluidic chip has the characteristics of controllable liquid flow, extremely less consumption of samples and reagents, ten-fold or hundred-fold improvement of analysis speed and the like, can simultaneously analyze hundreds of samples in a few minutes or even shorter time, and can realize the whole processes of pretreatment and analysis of the samples on line.
Droplet microfluidics is an important branch of microfluidic chip technology. Droplet microfluidics technology was developed over the traditional single-phase microfluidic chip technology, and three-inlet T-type microfluidic chip designs were first proposed by professor samagilov f Rustem, university of chicago and have gained widespread attention and use in the next few years. Compared with a single-phase micro-fluidic system, the system has the advantages of less consumption of samples and reagents, higher mixing speed, difficulty in causing cross contamination, easiness in operation 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-droplets have the advantages of high flux, no cross contamination and the like, and have great application potential in the fields of ink-jet printing, micro-mixing, DNA analysis, material synthesis, protein crystallization and the like.
For early diagnosis, the concentration of the analyte in the sample is usually very small, and the detection of a very small amount of sample (e.g., DNA, cells, bacteria, and biological proteins) usually poses a great challenge, so that the concentration of the sample is particularly important.
Electroosmotic flow driving technology is one of the important components of the microfluidic chip. The electroosmotic micro pump has the advantages of easiness in processing and controlling, no need of moving parts, high repeatability and reliability and the like. At present, electroosmotic flow is generally divided into two modes, direct current electroosmosis and alternating current electroosmosis. The development of the dc electroosmosis micropump is limited by the fact that several hundreds even thousands of volts are applied to the microchannel, which causes the electrochemical reaction between the electrode and the solution, the generation of bubbles, the joule heating effect, and the like.
Disclosure of Invention
In view of the above, the present invention provides a microfluidic chip, a device containing the microfluidic chip, and a sample concentration method. The invention aims to concentrate a sample and remove redundant liquid, and a microfluid chip is matched with an electrode to concentrate the sample.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a micro-fluidic 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 also provided with electrodes 4, and the electrodes 4 apply alternating current seepage disturbance force and/or dielectrophoresis force to the micro-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, and the electrode 4 comprises a middle electrode and two side electrodes, wherein the width of the middle electrode is 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 middle electrode is at least the width of the two side electrodes
And (4) doubling.
In some embodiments of the invention, the two electrodes are applied with voltages in phase and the middle electrode is applied with a voltage in anti-phase with the two electrodes.
In some embodiments of the invention, the frequency of the electrode 4 is: a flow field capable of generating an alternating current electroosmotic flow; and is capable of generating positive dielectrophoretic forces; and the disturbing force of alternating current seepage is larger than the positive dielectrophoresis force, so that particles with the diameter of less than 2 micrometers (d is less than 2 micrometers) are effectively controlled.
In some embodiments of the invention, the frequency of the electrode 4 is 1/2 π RmCD(ii) a Wherein R ismIs the resistance of the solution in the sample, CDIs 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 < 60 ° (the angle is preferably 30 ° for embodiments of the invention).
In other embodiments of the invention, the electrode 4 is a continuously skewed alternating current electrode; the frequency of the continuous deflection alternating current electrode can generate negative dielectrophoretic force, and particles with the diameter of more than 0.5 micrometer (d is more than 0.5 mu m) can be effectively controlled.
On the basis, the invention also provides a sample concentrating device which comprises the microfluidic chip.
The invention also provides the application of the microfluidic chip or the device in sample concentration; the sample comprises a mixture of one or more of nucleic acids, cells, bacteria, or proteins.
The invention also provides a method for concentrating a sample based on the microfluidic chip or the device, which comprises the following steps:
step 1: obtaining a sample based on a water-in-oil emulsion droplet state;
step 2: introducing the sample in the droplet state into the sample inlet 1;
and step 3: and adjusting the frequency of the electrode 4 to generate alternating current seepage disturbance force and/or dielectrophoresis force to concentrate the sample in the droplet state, cutting the sample through the acute angle between the outlets 2, and collecting the concentrated sample to reduce the liquid amount of the product droplets, thereby achieving the effect of improving the concentration of the sample to be detected in the droplets.
The beneficial effects of the invention include but are not limited to:
A. alternating current (ac) seepage is a method that does not affect the sample and is widely used to manipulate, concentrate, transport samples (DNA, cells, bacteria, biological proteins, etc.). Since the ac electroosmotic flow first disturbs the fluid to drive the sample by the fluid, the sample can be said to be kept in the original state.
B. According to the invention, under the continuous fluid (continuous flow) state, the relative area concentration of liquid drops is carried out by using alternating current seepage flow and positive dielectrophoresis force, and then the cutting of redundant liquid drops is carried out through an acute angle between outlets, so as to obtain concentrated sample liquid drops.
C. Concentrated droplet samples have a wide range of applications, and may be subjected to drug sensitive assays assuming the sample is a cell/bacterium or to analysis and culture after a small number of samples have been concentrated. If the sample is DNA, the efficiency of the subsequent amplification, analysis or hybridization (hybridization) can be effectively improved due to the high concentration in the droplets after concentration, and the reaction time can be shortened due to the increased collision probability caused by the increased concentration of the sample in the droplets.
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 illustrating the operation of a microfluidic chip according to the present invention; wherein FIG. 1a shows a schematic representation of the perturbing force and the positive dielectrophoretic force of an alternating electroosmotic flow; FIG. 1b shows that when the sample is DNA or protein, the blue curve is the disturbing force of the alternating current percolation, the green curve is the positive dielectrophoretic force to which the sample is subjected, and when the sample is concentrated, the frequency at which the disturbing force of the alternating current percolation is greater than the positive dielectrophoretic force is selected; FIG. 1c shows the blue curve representing the perturbing force of the AC percolation, the purple curve representing the positive dielectrophoretic force to which the sample is subjected, and the frequency at which the perturbing force of the AC percolation is greater than the positive dielectrophoretic force is selected when the sample is concentrated;
FIG. 2 is a schematic diagram of a microfluidic chip structure provided by the present invention; wherein FIG. 2A shows a top view; FIG. 2B shows a schematic view of electrode 4 in cross section (green dashed direction) of the tube; the structure and design of the chip are suitable for nucleic acid molecules, proteins, bacteria and other particles smaller than 2 microns;
FIG. 3 is a schematic diagram of a microfluidic chip for concentrating cells/bacteria by pure negative dielectrophoresis according to another embodiment of the present invention; the structure and design of the chip are suitable for particles with the size more than 0.5 micron and obvious dielectrophoresis force, such as bacteria, cells and the like;
wherein, 1-a sample inlet; 2-an outlet; 3-micro flow channel; 4-electrodes.
Detailed Description
The invention discloses a micro-fluidic chip, a device containing the micro-fluidic chip and a sample concentration method. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.
The microfluidic chip, the device containing the microfluidic chip and the parts, raw materials and reagents used in the sample concentration method provided by the invention are all commercially available.
The invention is further illustrated by the following examples:
the invention provides a micro-fluidic 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 also provided with electrodes 4, the electrodes 4 applying an alternating electroosmotic perturbation force and/or a dielectrophoretic force to the microchannels 3.
ACEO flow (AC electorosis flow) principle: the AC Electro-osmotic flow (ACEO) is caused by the interaction of the electric field component parallel to the planar electrode and the charged ions adjacent to the electrode surface, the coulombic forces (1-100 nm thick) charge on the electrode surfaceDue to the body. Electroosmotic flow velocity can be expressed by the Smoluchowski equation:
where ε is the dielectric constant of the fluid, η is the viscosity,
surface potential and E applied electric field strength. Under the condition of non-uniform surface charge (such as asymmetric electrodes), the electric charges in the electric double layer are no longer in Poisson-Boltzmann equilibrium and polarization phenomenon (polarization) occurs due to the alternating electric field and the control of the frequency thereof to an appropriate charging and discharging time constant. As a result, the applied electric field can penetrate the electric double layer to generate transient current, so that the electric double layer in the charge/discharge state acts as a capacitor. Since a large amount of electric charges (field-induced charges) induced on the surface of the electrode always keep the same direction with the electric field in the process that the alternating current electric field continuously changes directions in a periodic manner, the net flow of the fluid, namely alternating current seepage (ACEO), can be presented under the condition that the flow field is disturbed by the changes of the comprehensive and average charge density. While the electric field frequency ω plays a key role in manipulating the ac electroosmotic flow. If ω is too high, the electric double layer cannot form significant charge polarization exchange to cause flow because the electric field charges and discharges the electric double layer for too short a time. However, if ω is too low, the electrical double layer has a strong shielding (screening) effect on the applied electric field, such that the charge/discharge characteristic time of the circuit acting on the tangential direction of the charge in the current layer and the resistance: τ ═ RmCDFrequency f-1/2 π RmCDWherein R ismIs the resistance of the solution, CDElectric double-layer capacitance: cD～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 double electric layers 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: the arrangement of charge carriers is known as an electrical double layer, where a voltage is applied to an upstanding electrode in contact with the electrolyte and oppositely charged ions accumulate at the electrode surface.
Under the mechanism of alternating electric field, the polarized dielectric particles generate dielectrophoresis under the action of dipole moment. The magnitude of the dielectrophoretic force and velocity can be obtained according to the electromagnetic field polarization theory.
After an alternating electric field is introduced into the microfluidic chip, fluid can generate internal flow under the action of the alternating electric field, and the internal flow is represented as local vortex in a flow field or directional net flow of the fluid. Dielectrophoresis (DEP) technology is an important means of manipulating micro-nano-scale dielectric particles, by which different species 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 various factors such as the conductivity of the fluid, an electrode structure, the external electric field, an external light source or a heat source and the like; the magnitude and direction of the dielectrophoresis force of the micro-nano particles are influenced by various factors such as dielectric constant and conductivity of fluid media and particles, particle radius, electric field distribution voltage amplitude and frequency and the like. Under the same condition, the dielectrophoresis force is exponentially attenuated with the increase of the distance between the particles and the electrodes, only dielectric particles in the area near the electrodes show a remarkable dielectrophoresis effect, and the particle dielectrophoresis phenomenon of submicron or nanometer scale is weaker.
Submicron and nanoscale particles, or particles outside the range in which the dielectrophoretic effect works effectively, sometimes exhibit significant dielectrophoretic effects at relatively low electric field strengths. This shows 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 located. Due to the presence of vortices inside the fluid, particles that are further from the electrodes are transported to the region near the electrodes and are thus acted upon by dielectrophoretic forces. The invention takes three-level asymmetric alternating current electrode dielectrophoresis behavior of micro-nano particles 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 invention, the electrode 4 is an asymmetric alternating current electrode. Preferably, the asymmetric electrode is a three-step asymmetric electrode comprising a middle electrode and two side electrodes, and the width of the middle electrode is larger than that of the two side electrodes. Preferably, the intermediate electrodeIs at least 2 times the width of the two-sided electrodes. More preferably, the width of the middle electrode is at least the width of the two side electrodes
And (4) doubling. Preferably, the two side electrodes are applied with voltages in the same phase, and the middle electrode is applied with a voltage in the opposite phase to the two side electrodes.
In some embodiments of the invention, the frequency of the electrode 4 is: a flow field capable of generating an alternating current electroosmotic flow; and is capable of generating positive dielectrophoretic forces; and the disturbing force of alternating current seepage is greater than the positive dielectrophoresis force. Preferably, the frequency of the electrode 4 is 1/2 π RmCD(ii) a Wherein R ismIs the resistance of the solution in the sample, CDIs an electric double-layer capacitor.
The present invention mainly provides a three-stage asymmetric electrode, wherein the width of the central wide electrode is designed to be more than 2 times of the width of the two thinner electrodes, so that the eddy current disturbance effect generated by the alternating current seepage can concentrate the net flow to the central large electrode because the eddy current generated by the central wide electrode is larger than the eddy current generated by the two thinner electrodes, and finally the particles to be measured (such as DNA, protein, bacteria, etc.) in the liquid drop are concentrated at the fluid stagnation point in the center of the wide electrode, as shown in FIG. 1 (a). The ACEO intensity is dependent on RC time, i.e. frequency dependent (f 1/2 π R)mCD) Too high of 1/2 π R, as beforemCDThe frequency of the (A) is that the charging and discharging time of the electric double layer by the electric field is too short, the electric double layer cannot form obvious charge polarization exchange to cause flow, and the ACEO effect and the flow field are quite weak; too low as 1/2 pi RmCDThe frequency flow field also has a strong shielding effect on the applied electric field due to the electric double layer, so that Maxwell force acting on the tangential direction of charges in the electric double layer is weakened or insufficient to drive the fluid. Therefore, ACEO is only applied in the frequency range of 1/2 π RmCDHas a significantly faster flow field effect near the frequency range, and also has a dielectrophoretic effect due to the application of an alternating electric field, and most preferably, if the mechanism responsible for the frequency is present in a positive dielectrophoretic force, an adsorption force is provided to move the target particles/molecules towards the electrode surfaceThe attraction is concentrated, if the action of ACEO is matched, the speed of the ACEO for bringing the target particles into the surface of the central electrode can be increased, and after the target particles enter the central fluid stagnation point on the surface of the central wide electrode, the target particles can be maintained at the center due to positive dielectrophoresis force and are not easily brought out by a flow field, so the frequency condition of the electric field for optimally concentrating the particles/molecules in the center of the liquid drop is as follows:
1. obvious alternating current induces ACEO flow field; and is
2. Simultaneously generating positive dielectrophoresis force; and is
3. The ACEO flow field force is greater than the positive dielectrophoretic force, as 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; continuously skewing the frequency of the ac electrodes can produce negative dielectrophoretic forces.
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 the application of the microfluidic chip or the device in sample concentration; 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 in detail.
The invention also provides a method for concentrating a sample based on the microfluidic chip or the device, which comprises the following steps:
step 1: obtaining a sample in an emulsified droplet state;
step 2: introducing a sample in a liquid drop state into the sample inlet 1;
and step 3: and adjusting the frequency of the electrodes 4 to generate alternating current seepage disturbance force and/or dielectrophoresis force to concentrate the sample in the droplet state, cutting the sample through the acute angle between the outlets 2, and removing redundant liquid in the droplets to collect the concentrated sample.
The working principle of the microfluidic chip provided by the invention is as follows: referring to fig. 2, for example, a concentrated DNA solution is used as a sample, the sample is first converted into an emulsified droplet state and then injected into the chip, so that the droplet fills the channel, and then the droplet is subjected to an alternating current (AC Electro-osmos, ACEO) perturbing force and a dielectrophoresis force (dielectrophoresis) generated by an asymmetric electrode, so as to bring a target (DNA, cells, bacteria, etc.) in the droplet to a stagnation region of a central electrode in the channel, wherein the stagnation region is limited by a counter balance between the alternating current (AC Electro-osmos) and the dielectrophoresis, and in an ideal state, all the samples are concentrated in a middle region of the central electrode, and finally the droplet is cut by an acute angle of an outlet structure when the droplet is moved to an outlet, so that the concentrated sample can be collected, and the design can effectively concentrate the target (DNA) in the droplet for detection, RNA, proteins, bacteria, cells, etc.) and reduced volume may be used in conjunction with subsequent biochemical reaction experiments to simultaneously reduce the amount of reagent required.
The design of the asymmetric electrode (fig. 2B) is changed based on the basic structure of alternating current seepage, the basic pattern is that a circulating flow field disturbance solution is generated when the symmetric electrode operates, the electrode is designed into the asymmetric pattern based on the phenomenon, at the moment, the fluid phenomenon can generate a stagnation area in a partial area on the electrode after antagonism due to the fact that the flow field disturbance force generated by the asymmetric electrode is different in size and the positive dielectrophoresis attraction force generated by the induced particles on the surface of the electrode is added. If the flow field turbulence force is larger than the particle positive dielectrophoresis attraction force, the target object is concentrated on the middle area of the central electrode by the strong flow field turbulence force, and the weak positive dielectrophoresis force adsorbs the particles on the surface of the electrode, so that the target object is concentrated on a small area, if the flow field turbulence force is smaller than the particle positive dielectrophoresis attraction force, the target object is brought to the central electrode by the weak flow field turbulence force, but the strong positive dielectrophoresis force pulls the particles away from the central area of the electrode and adsorbs the particles on the edge of the electrode (the edge of the electrode is a strong electric field area), the invention achieves the concentrated target through the area.
In other embodiments of the invention, as shown in FIG. 3, the negative dielectrophoretic repulsion forces generated by the continuously deflecting electrodes are used to concentrate the particles into the center of the conduit to remove excess fluid through the outlet structure, with the size of the concentrated region being positively correlated with the distance between the deflecting electrodes, with the larger (smaller) distance between the deflecting electrodes being larger (smaller) than the concentrated region, and with the dielectrophoretic forces acting only in the areas of high electric field and the electric field decaying exponentially so that the range of influence is only around the electrodes. However, this method can only affect the particle samples with size larger than 500nm (d >500nm) to have insufficient force for small molecule samples, for example, since the volume of biological protein and DNA is nanometer level, the dielectrophoresis force is too weak, such samples cannot be effectively manipulated, and therefore, the samples cannot be concentrated.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. A micro-fluidic 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 disturbance force and/or dielectrophoresis force to the micro-channel (3);
the electrode (4) is an asymmetric alternating current electrode.
2. The microfluidic chip according to claim 1, wherein the electrodes (4) are three-level asymmetric electrodes, and the electrodes (4) comprise a middle electrode and two side electrodes, and the width of the middle electrode is greater than the width of the two side electrodes.
3. The microfluidic chip of claim 2, wherein the width of the middle electrode is at least 2 times the width of the two side electrodes.
4. Microfluidic chip according to claim 3, characterized in that the frequency of the electrodes (4) is: a flow field capable of generating an alternating current electroosmotic flow; and is capable of generating positive dielectrophoretic forces; and the disturbing force of alternating current seepage is greater than the positive dielectrophoresis force.
5. Microfluidic chip according to claim 4, characterized in that the frequency of the electrodes (4) is 1/2 π RmCD(ii) a Wherein R ismIs the resistance of the solution in the sample, CDIs an electric double-layer capacitor.
6. Microfluidic chip according to claim 5, wherein the number of outlets (2) is at least 2, and the included angle between 2 adjacent outlets (2) is < 60 °.
7. Microfluidic chip according to claim 1, characterized in that said electrodes (4) are continuous skewed alternating current electrodes; the frequency of the continuously biased ac electrode is capable of generating a negative dielectrophoretic force.
8. A device for concentrating a sample, comprising the microfluidic chip according to any one of claims 1 to 7.
9. Use of a microfluidic chip according to any of claims 1 to 7 or a device according to claim 8 for concentrating a sample; the sample comprises a mixture of one or more of nucleic acids, cells, bacteria, or proteins.
10. A method for concentrating a sample based on a microfluidic chip according to any one of claims 1 to 7 or a device according to claim 8, comprising the steps of:
step 1: obtaining a sample of the droplet state;
step 2: introducing the sample in the droplet state into the sample inlet (1);
and step 3: and adjusting the frequency of the electrodes (4), generating alternating current electroosmotic flow disturbance force and/or dielectrophoresis force to concentrate the samples in the droplet state, cutting by the acute angle between the outlets (2), and collecting.
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| CN111912697A (en) * | 2020-08-14 | 2020-11-10 | 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 |
| WO2024007891A1 (en) * | 2022-07-07 | 2024-01-11 | 珠海捷壹生物科技有限公司 | Microfluidic system for controlling movement of charged particles and control method |
| WO2024007892A1 (en) * | 2022-07-07 | 2024-01-11 | 珠海捷壹生物科技有限公司 | Device for controlling charged particles in fluid and method for controlling movement of charged particles |
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