CN105457692B - Microfluidic separation device and method - Google Patents
Microfluidic separation device and method Download PDFInfo
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- CN105457692B CN105457692B CN201610006104.2A CN201610006104A CN105457692B CN 105457692 B CN105457692 B CN 105457692B CN 201610006104 A CN201610006104 A CN 201610006104A CN 105457692 B CN105457692 B CN 105457692B
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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
- B01L3/502753—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 bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
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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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L2200/0652—Sorting or classification of particles or molecules
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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
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Abstract
The invention discloses a microfluidic separation device and method, and belongs to the field of microfluidic. The device and method are used for separating mixed neutral particles in an electrolyte solution. The device comprises a first fluid driving micropump, a separation unit and a second fluid driving micropump. The first fluid driving micropump comprises first fluid driving microelectrodes used for driving an electrolyte solution inside the first fluid driving micropump to transversely flow at first preset flow speed, the separation unit comprises sample separation microelectrodes used for generating an uneven electric field, the second fluid driving micropump comprises second fluid driving microelectrodes used for driving an electrolyte solution inside the second fluid driving micropump to flow transversely at second preset flow speed, and the second preset flow speed is distributed in the longitudinal direction in a gradient mode. The microfluidic separation device and method achieve transportation and separation of the mixed neutral particles, no valves and no mechanical components are used in the transportation and separation process, the cost is low, and miniaturization of the microfluidic separation device is facilitated.
Description
Technical field
The present invention relates to micro-fluidic field, in particular to a kind of microfluidic separation device and method.
Background technology
Micro-full analytical system (Miniaturized Total Analysis System, μ-TAS), is also called " chip
Laboratory (Lab-on-a-chip) ", is such as cell, pretreatment of colloidal particles, defeated by sample, especially neutral corpuscle
The Routine Test Lab operation such as fortune, separation and detection is integrated in size and is completed on the chip of square centimeter level, with analysis efficiency
Height, sample consumption reduction, small volume, it is easy to integrated to wait remarkable advantage.Micro-fluidic chip is the heat of " chip lab " development
Point field, has broad application prospects, and has penetrated into clinical medicine, bio-pharmaceuticals, molecular biology, judicial expertise, food
Product health and the every field such as environment measuring and the detecting of biological weapons.Wherein, sample transport and separate be analysis detection
Key link, is integrated in micro-fluidic chip, and miniaturization, automation and the portability for realizing bio-analysis system have
It is significant.In existing micro-fluidic chip, mix the sample introduction of neutral corpuscle sample and to transport be by Miniature injection pump reality
Existing, this mode is relatively costly, and is unfavorable for the miniaturization to realize microfluidic separation device integrated with separative element.
The content of the invention
It is micro- by designing first fluid driving it is an object of the invention to provide a kind of microfluidic separation device and method
Pump, separative element and second fluid drive Micropump, and transporting for neutral hybrid fine particles is integrated with disjoint set, above-mentioned to improve
Problem.
In a first aspect, a kind of microfluidic separation device provided in an embodiment of the present invention, for separating electrolyte solution in
Mixing neutral corpuscle, including：First fluid drives Micropump, separative element and second fluid to drive Micropump；The first fluid drives
Dynamic Micropump includes that first fluid drives microelectrode, the separative element to separate microelectrode including sample, and the second fluid drives
Micropump includes that second fluid drives microelectrode, the first fluid to drive microelectrode and the second fluid to drive microelectrode to be
Asymmetric electrode；
It is micro- to drive the first fluid to drive that the first fluid drives microelectrode to be used for the first inhomogeneous field of generation
Electrolyte solution in pump is with the first preset flow rate lateral flow to the separative element；
The sample separates microelectrode to be used to produce the second inhomogeneous field that the mixing neutrality in the separative element is micro-
Grain is separated in a longitudinal direction；
The second fluid drives microelectrode to be used for the 3rd inhomogeneous field of generation and is flowed into by the separative element with driving
It is many in the mixing neutral corpuscle for separating in a longitudinal direction in electrolyte solution in the second fluid driving Micropump
Neutral corpuscle is planted successively to be flowed out in chronological order with the second preset flow rate, wherein, second preset flow rate is in along the longitudinal direction
Gradient is distributed.
With reference in a first aspect, the embodiment of the present invention additionally provides the first possible embodiment of first aspect, wherein, institute
Stating microfluidic separation device also includes cover plate and substrate, and the cover plate covered and formed on the substrate for electrolyte solution stream
Dynamic microchannel, the microchannel includes that the first fluid being sequentially communicated drives microchannel, separates microchannel and second fluid drive
Dynamic microchannel, the first fluid drives microchannel to be located at the first fluid and drives in Micropump, and the separation microchannel is located at
In the separative element, the second fluid drives microchannel to be located at the second fluid and drives in Micropump, the first fluid
Microelectrode, sample separation microelectrode and the second fluid is driven to drive microelectrode to be successively set on first fluid driving micro-
Passage, separation microchannel and second fluid are driven on the substrate of microchannel bottom.
With reference to the first possible embodiment of first aspect, the embodiment of the present invention additionally provides second of first aspect
Possible embodiment, wherein, distribution gradient is specially second preset flow rate along the longitudinal direction：With away from the second
Body drives the increase of microelectrode surface longitudinal distance, and second preset flow rate first increases, then reduces, and Gaussian Profile is presented.
May implement with reference to the first possible embodiment of first aspect or first aspect or second of first aspect
Mode, the embodiment of the present invention additionally provides the third possible embodiment of first aspect, wherein, the first fluid drives micro-
Electrode and the second fluid drive microelectrode to be asymmetric interdigital parallel array electrode, and the asymmetric interdigital is parallel
Array electrode includes small electrode and large electrode, and the small electrode is in periodic distribution according to default spacing with the large electrode.
With reference to the third possible embodiment of first aspect, the embodiment of the present invention additionally provides the 4th kind of first aspect
Possible embodiment, wherein, the sample separates microelectrode includes interdigital parallel array electrode.
With reference in a first aspect, the embodiment of the present invention additionally provides the 5th kind of possible embodiment of first aspect, wherein, institute
State first fluid and drive Micropump including exchanging electric osmose Micropump.
With reference in a first aspect, the embodiment of the present invention additionally provides the 6th kind of possible embodiment of first aspect, wherein, institute
Stating first fluid driving Micropump includes AC Electric Heater Micropump.
With reference in a first aspect, the embodiment of the present invention additionally provides the 7th kind of possible embodiment of first aspect, wherein, institute
State second fluid and drive Micropump including exchanging electric osmose Micropump.
With reference in a first aspect, the embodiment of the present invention additionally provides the 8th kind of possible embodiment of first aspect, wherein, institute
Stating microfluidic separation device also includes AC driven power, and the AC driven power includes the first AC driven power, second
AC driven power and the 3rd AC driven power, first AC driven power are used to drive micro- electricity for the first fluid
Pole provides alternating potential, and second AC driven power is used to provide alternating potential for the sample separates microelectrode, described
3rd AC driven power drives microelectrode to provide alternating potential for the second fluid.
A kind of second aspect, microfluidic separation method provided in an embodiment of the present invention, is applied to microfluidic separation device, institute
Stating microfluidic separation device includes：First fluid drives Micropump, separative element and second fluid to drive Micropump；The first fluid
Driving Micropump includes that first fluid drives microelectrode, the separative element to separate microelectrode including sample, and the second fluid drives
Dynamic Micropump includes that second fluid drives microelectrode, the first fluid to drive microelectrode and the second fluid to drive microelectrode equal
It is asymmetric electrode；Methods described includes：
The first fluid drives microelectrode to produce the first inhomogeneous field to drive the first fluid to drive in Micropump
Electrolyte solution with the first preset flow rate lateral flow to the separative element；
The sample separates microelectrode and produces the second inhomogeneous field that the mixing neutral corpuscle in the separative element exists
Separated on longitudinal direction；
The second fluid drives microelectrode to produce the 3rd inhomogeneous field to drive described in the separative element is flowed into
Second fluid drive Micropump in electrolyte solution in separate in a longitudinal direction mixing neutral corpuscle in it is various in
Property particulate successively flowed out in chronological order with the second preset flow rate, wherein, second preset flow rate is along the longitudinal direction in gradient
Distribution.
The present invention devises first fluid and drives Micropump, separative element and second fluid to drive Micropump, by first fluid
Drive Micropump to realize that mixing neutral corpuscle is transported, by separative element realize different types of neutral corpuscle in device longitudinal direction
The separation in direction, i.e., different types of neutral corpuscle is suspended at the different height for separating microelectrode surface apart from sample, is passed through
Second fluid drive device causes that the neutral corpuscle at different hoverheights obtains different lateral velocities, so that in chronological order
Successively flow out.Wherein, first fluid driving Micropump, separative element and second fluid driving Micropump can be integrated in same miniflow
On control chip, to realize mixing transporting and separating for neutral corpuscle.
With prior art compared with Miniature injection pump is realized by way of sample transport, transport with separation process valveless without
Mechanical part, and simple and easy to apply, low cost, controllability are strong, be easily integrated, and are conducive to the miniaturization of microfluidic separation device.
Other features and advantages of the present invention will illustrate in subsequent specification, also, partly become from specification
It is clear that or being understood by implementing the embodiment of the present invention.The purpose of the present invention and other advantages can be by being write
Specifically noted structure is realized and obtained in specification, claims and accompanying drawing.
Brief description of the drawings
In order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to institute in embodiment
The accompanying drawing for needing to use is briefly described, it should be apparent that, drawings in the following description are only some implementations of the invention
Example, for those of ordinary skill in the art, on the premise of not paying creative work, can also obtain according to these accompanying drawings
Obtain other accompanying drawings.By the way that shown in accompanying drawing, above and other purpose of the invention, feature and advantage will become apparent from.In whole
Identical reference indicates identical part in accompanying drawing.Deliberately accompanying drawing, emphasis are not drawn by actual size equal proportion scaling
It is that purport of the invention is shown.
Fig. 1 shows a kind of planar structure schematic diagram of microfluidic separation device provided in an embodiment of the present invention；
Fig. 2 shows a kind of a kind of implementation method of the separative element of microfluidic separation device provided in an embodiment of the present invention
Principle schematic；
Fig. 3 shows a kind of another embodiment party of the separative element of microfluidic separation device provided in an embodiment of the present invention
The principle schematic of formula；
Fig. 4 shows the dimensional structure diagram of another microfluidic separation device provided in an embodiment of the present invention；
Fig. 5 shows a kind of method flow diagram of microfluidic separation method provided in an embodiment of the present invention.
In figure, reference is respectively：
Substrate 110；Cover plate 120；Injection port 210；Outlet 220；First fluid drives Micropump 300；First fluid drives
Microelectrode 310；Separative element 400；Sample separates microelectrode 410；Second fluid drives Micropump 500；Second fluid drives micro- electricity
Pole 510；AC driven power 600；First neutral corpuscle 710；Second neutral corpuscle 720.
Specific embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete
Whole description, it is clear that described embodiment is only a part of embodiment of the invention, rather than whole embodiments.It is based on
Embodiment in the present invention, it is every other that those of ordinary skill in the art are obtained under the premise of creative work is not made
Embodiment, belongs to the scope of protection of the invention.
A kind of microfluidic separation device is the embodiment of the invention provides, it is micro- for separating the mixing neutrality in electrolyte solution
Grain, the mixing neutral corpuscle is made up of different types of neutral corpuscle.As shown in figure 1, the microfluidic separation device is main
Including：First fluid drives Micropump 300, separative element 400 and second fluid to drive Micropump 500.Wherein, first fluid drives micro-
Pump includes that first fluid drives microelectrode, separative element 400 to separate microelectrode including sample, and second fluid drives Micropump 500 to wrap
Include second fluid and drive microelectrode.It should be noted that the first fluid drives microelectrode and second fluid driving micro-
Electrode is asymmetric electrode.The first fluid drives microelectrode for producing the first inhomogeneous field to drive described first
Fluid drives the electrolyte solution in Micropump with the first preset flow rate lateral flow to the separative element 400.The sample
Separate microelectrode be used for produce the second inhomogeneous field by the mixing neutral corpuscle in the separative element 400 in a longitudinal direction
Separate.The second fluid drives microelectrode for producing the 3rd inhomogeneous field to drive by the separative element 400
Flow into the mixing neutral corpuscle for separating in a longitudinal direction during the second fluid drives the electrolyte solution in Micropump 500
In various neutral corpuscles successively flowed out in chronological order with the second preset flow rate, wherein, second preset flow rate is along longitudinal direction
Direction distribution gradient.
For example, first fluid driving Micropump 300 can ooze Micropump for alternating current, now, the electrical conductivity of electrolyte solution can
Think 0.001-0.085S/m, first fluid to drive and be applied with 100Hz- respectively on any two adjacent electrode of microelectrode
The phase of 100kHz differs the sinusoidal alternating potential of 180 degree, produces the first inhomogeneous field, micro- containing mixing neutrality to be separated
After the electrolyte solution of grain enters first fluid driving Micropump 300, first fluid drives microelectrode surface to form electric double layer so that
Multiple contrary sign ions in diffusion layer in electric double layer slide in the presence of electric field force, and surrounding solvent molecule is due to viscous
Property effect be driven motion, due to first fluid drive microelectrode 310 adjacent electrode be asymmetric microelectrode so that it is first-class
Body drives the electrolyte solution containing mixing neutral corpuscle to be separated in Micropump 300 with the first preset flow rate lateral flow,
Into separative element 400.
Additionally, it can also be AC Electric Heater Micropump, now, the electrical conductivity of electrolyte solution that first fluid drives Micropump 300
Can be 0.085-0.1S/m.First fluid to drive and be applied with alternating potential on microelectrode, is specifically as follows：First fluid drives
An electrode in any two adjacent electrode of microelectrode 310 applies sinusoidal alternating potential, another electrode ground connection.Alternation electricity
The frequency of gesture can be 100kHz-1MHz.First fluid drives microelectrode to produce the first inhomogeneous field, is mixed containing to be separated
After the electrolyte solution of conjunction neutral corpuscle enters first fluid driving Micropump 300, the inhomogeneous field can cause electrolyte molten
The thermograde of liquid, in turn results in the change of the electrical conductivity and dielectric constant of electrolyte solution, final to produce the electric heating stream for orienting
It is dynamic so that the electrolyte solution containing mixing neutral corpuscle to be separated presets stream with first during first fluid drives Micropump 300
Fast lateral flow, into separative element 400.
It should be noted that when first fluid drives Micropump 300 for exchange electric osmose Micropump, AC Electric Heater flowing is while depositing
, simply the electrical conductivity of electrolyte solution and the frequency of alternating potential determine that exchange electrokinetic flow accounts for leading role.And by
It is identical in the flow direction of EOF and the flow direction of alternating current hot-fluid is exchanged, therefore, the appearance of electric heating flowing effect
The performance of exchange electric osmose Micropump can be improved.
Wherein, frequency, the amplitude of the first preset flow rate and alternating potential, the electrical conductivity of electrolyte solution, first fluid drives
The width ratio of the width, spacing and adjacent electrode of dynamic microelectrode, first fluid drives the height of microchannel in Micropump 300 relevant.
Exchange electric osmose Micropump or AC Electric Heater Micropump drive Micropump 300 to have and make simply, without movement as first fluid
The advantage that part, controllability are strong, be easily integrated, and exchange type of drive does not need high drive, in the absence of electrolysis etc.
Problem, is a kind of convenient, quick, efficient, inexpensive microfluid transport technique.
Electrolyte solution containing mixing neutral corpuscle to be separated is under the transport effect that first fluid drives Micropump 300
After flowing into separative element 400, the direction flowing that second fluid drives Micropump 500 is on the one hand continued towards in the presence of inertia；
On the other hand, separative element 400 can realize the separation in a longitudinal direction of different types of mixing neutral corpuscle.
Separative element 400 realizes that the concrete principle of the separation in a longitudinal direction of different types of mixing neutral corpuscle can
Think：Sample separates and the sinusoidal alternating potential that phase differs 180 degree is applied with any two adjacent electrode of microelectrode, i.e. ,+
V0Sin (ω t) and-V0sin(ωt).In order to reducing alternating current blends centrifugation of the AC Electric Heater to separative element 400 as far as possible
Influence, sample separate microelectrode on apply alternating potential the preferred 100kHz-10MHz of frequency, the conductance of electrolyte solution
Rate is preferably 0.001-0.085S/m, i.e. first fluid and drives Micropump 300 to be preferably exchange electric osmose Micropump.Separative element 400
Sample separates microelectrode to be used to produce the second inhomogeneous field, different types of mixing neutral corpuscle to be in the second inhomogeneous field
In due to polarity effect will respectively produce directional migration motion, i.e., acted on by dielectrophoresis.
Now, to separative element 400 in different types of mixing neutral corpuscle carry out force analysis understand, electrolyte is molten
Different types of mixing neutral corpuscle in longitudinal direction, i.e. z-axis direction, mainly by dielectrophoretic force, make by gravity, buoyancy in liquid
With.Therefore separative element 400 realizes that the separation in a longitudinal direction of different types of mixing neutral corpuscle has two kinds of implementations：
Assuming that mixing neutral corpuscle is two different kinds of neutral corpuscle, respectively the first neutral corpuscle 710 and the second neutral corpuscle
720。
The first implementation method is：Regulation is applied to the frequency and width of the sinusoidal alternating potential on sample separation microelectrode
Value so that the first neutral corpuscle 710 is separated microelectrode surface by the sample that positive dielectrophoretic force acts on the bottom of separative element 400
Edge is enriched with；Second neutral corpuscle 720 is subject to sufficiently large negative dielectrophoretic force to act on, and is enriched in and separates microelectrode apart from sample
The certain altitude h on surfacepPlace, as shown in Fig. 2 to realize longitudinal direction of two kinds of mixing neutral corpuscles in separative element 400, i.e.,
The separation on z-axis direction shown in Fig. 2.
Second implementation method be：Regulation is applied to the frequency and width of the sinusoidal alternating potential on sample separation microelectrode
Value so that the first neutral corpuscle 710 and second it is neutral it is micro- acted on by negative dielectrophoretic force, due to the first neutral corpuscle 710 and the
Two neutral micro- density, dielectric property are different with electrical conductivity, and it is single to be enriched in separation under the effect of different size of negative dielectrophoretic force
At different height in unit 400, h as shown in Figure 3p1And hp2, to realize two kinds of mixing neutral corpuscles in separative element 400
Longitudinal direction, i.e., the separation on z-axis direction shown in Fig. 3.Specifically chosen which kind of implementation method by the first neutral corpuscle 710,
The dielectric property and electrical conductivity of the dielectric constant of the second neutral corpuscle 720 and electrolyte solution are determined, for example, working as electrolyte solution
Dielectric constant be in when between the first neutral corpuscle 710 and second neutral micro- dielectric constant, the first can be selected to implement
Mode, when the first neutral corpuscle 710 and second it is neutral it is micro- be all higher than or less than electrolyte solution dielectric constant when, can select
Second implementation method.Certainly, then species can also be various to mixing neutral corpuscle, in particular to more than two kinds, now need
Change is applied to the frequency and amplitude that sample separates the sinusoidal alternating potential on microelectrode, realizes separating successively, specific embodiment party
Principle is identical when formula is with two kinds of mixing neutral corpuscles, does not repeat herein.
The separative element 400 of the embodiment of the present invention make use of dielectrophoresis principle, relative to other mechanical or optical grains
Son manipulation and separation method, easy to operate, fast response time simple with process, it is easy to accomplish what is be miniaturized and automate is excellent
Point, has greatly latent in for the accurate capture, enrichment, Separation Research of some neutral macromolecular particulates and biological cell
Power.
Electrolyte solution is followed used in different types of neutral corpuscle that longitudinal direction is separated by separative element 400
Property the effect lower second fluid that flows into drive Micropump 500, second fluid drives Micropump 500 to drive and described is separated in longitudinal direction
Successively the specific embodiment of outflow can be different types of neutral corpuscle in chronological order：First fluid drives Micropump 300
Micropump can be oozed for alternating current, first fluid to drive and be applied with 100Hz- respectively on any two adjacent electrode of microelectrode
The phase of 100kHz differs the sinusoidal alternating potential of 180 degree, produces the 3rd inhomogeneous field.Second fluid drives Micropump 500 to drive
Dynamic first fluid drives the electrolyte solution containing mixing neutral corpuscle to be separated in Micropump 300 horizontal with the second preset flow rate
To flowing, second preset flow rate distribution gradient along the longitudinal direction.So allow for being indulged during second fluid drives Micropump 500
The different types of neutral corpuscle separated to direction obtains different transverse flow speeds, so that successively flow out in chronological order, it is real
Show different types of neutral corpuscle in a lateral direction, i.e., the separation on x-axis direction.
Microfluidic separation device provided in an embodiment of the present invention, Micropump 300, separative element 400 are driven by first fluid
And second fluid drives Micropump 500 to realize transporting and separating for different types of mixing neutral corpuscle, transports and separation process
Valveless mechanical part, and simple and easy to apply, low cost, controllability are strong, be easily integrated, and are conducive to the micro- of microfluidic separation device
Type.
Microfluidic separation device provided in an embodiment of the present invention also includes cover plate 120 and substrate 110, as shown in figure 4, cover plate
120 cover the microchannel formed on the substrate 110 for electrolyte solution flowing.The microchannel includes what is be sequentially communicated
First fluid drives microchannel, separates microchannel and second fluid driving microchannel, and the first fluid drives microchannel to be located at
First fluid is driven in Micropump 300, and the separation microchannel is located in separative element 400, and the second fluid drives microchannel
Driven in Micropump 500 positioned at second fluid.First fluid drives microelectrode 310 to be arranged on first fluid and drives microchannel bottom
On substrate 110, sample separates microelectrode 410 and is arranged on the substrate 110 for separating microchannel bottom, and second fluid drives microelectrode
510 are arranged on second fluid drives on the substrate 110 of microchannel bottom.
It should be noted that in the embodiment of the present invention, substrate 110 can be preferably glass or silicon base, and cover plate 120 can
To be preferably dimethyl silicone polymer cover plate 120, first fluid drives microelectrode 310, sample to separate microelectrode 410 and second
Body drives microelectrode 510 to be processed into by micro-electromechanical technology technique, can select the good metal of electric conductivity as electrode material
Material, such as gold or titanium/gold are compound, and processing thickness can be hundreds of nanometers.The microchannel can be by micro-electromechanical technology work
Skill is processed on cover plate 120 or substrate 110, and depth can be designed as 50-200 μm.Additionally, sample introduction can be designed on cover plate 120
Mouth 210 and outlet 220, it is different types of after being respectively used to the input containing different types of mixing neutral corpuscle and separating
The output of neutral corpuscle.
Wherein, first fluid driving microelectrode 310 and second fluid driving microelectrode 510 can be preferably non-homogeneous fork
Finger formula parallel array electrode is, it is necessary to explanation, interdigital electrode is the electricity for having periodic patterns in face such as finger-like or pectination
Pole.As shown in figure 4, the asymmetric interdigital parallel array electrode include small electrode and large electrode, the small electrode with it is described
Large electrode is in periodic distribution according to default spacing.The width of the large electrode can be designed as 50~100 μm, the small electrode
Width can be designed as 10~40 μm.When using, applied respectively on the small electrode and large electrode that first fluid drives microelectrode 310
Plus the phase of 100Hz-100kHz differs the sinusoidal alternating potential of 180 degree, first fluid is driven to contain mixing in driving microchannel
The electrolyte solution of neutral corpuscle is in the case where electroosmosis is exchanged with the first preset flow rate lateral flow, i.e., the x-axis shown in Fig. 4
Direction flows, into separation microchannel.Apply respectively on the small electrode and large electrode that second fluid drives microelectrode 510
The phase of 100Hz-100kHz differs the sinusoidal alternating potential of 180 degree, the separated list in driving second fluid to drive microchannel
First 400 longitudinal directions, i.e., different types of mixing neutral corpuscle that the z-axis direction shown in Fig. 4 is separated is in exchange electric osmose
Successively flowed out in chronological order with the second preset flow rate under effect.Now, first fluid drives Micropump 300 and second fluid to drive
The overall flow direction of the electrolyte solution containing mixing neutral corpuscle in Micropump 500 flows to large electrode by small electrode.Need
It is bright, the size of additional sinusoidal alternating potential, frequency, small electrode width, large electrode width, default spacing and large and small electricity
The width of pole is first more pre- in first fluid drives microchannel than being electrolyte solution of the influence containing mixing neutral corpuscle
If the key factor of flow velocity and the second preset flow rate in second fluid drives microchannel.
The purpose of so design is that non-homogeneous interdigital parallel array electrode has non-homogeneous electricity that is easy to process, producing
The larger advantage in field, is conducive to improving the first preset flow rate and second preset flow rate.Certainly, first fluid drives microelectrode
310 and second fluid drive microelectrode 510 to may be designed in other and can drive the electrode structure of fluid lateral flow.
In the embodiment of the present invention, distribution gradient is specifically as follows second preset flow rate along the longitudinal direction：With away from
Second fluid drives the increase of the surface longitudinal distance of microelectrode 510, and second preset flow rate first increases, then reduces, and presents
Gaussian Profile.Can so cause the different types of neutral corpuscle separated on z-axis direction with the flowing of electrolyte solution
Different x-axis direction flow velocitys are obtained, is gradually disengaged in second fluid drives the x-axis direction motion process of microchannel and come, most
Successively flow out sequentially in time eventually.
In addition, sample separates microelectrode 410 can be preferably symmetrical interdigital parallel array electrode as shown in Figure 4, and
Spacing between electrode width and adjacent electrode can be designed as 10-100 μm.Symmetrically interdigital parallel array electrode has and adds
The advantage that work is convenient, inhomogeneous field that is producing is larger, what the mixing neutral corpuscle for being conducive to increase to separate in microchannel was subject to
Dielectrophoretic force.Certainly, sample separates microelectrode 410 and may be designed in other electrode structures, such as fort formula electrode structure etc..Need
It is noted that embodiment of the present invention kind, sample separates the second inhomogeneous field that microelectrode 410 produces and causes that separative element can
Will separate the different types of mixing neutral corpuscle flowed through in microchannel in longitudinal direction, i.e. z-axis direction separates, to sample
The particular number that product separate the electrode pair of microelectrode 410 is not limited.
Additionally, microfluidic separation device provided in an embodiment of the present invention can also include AC driven power 600, exchange is driven
Dynamic power supply 600 includes the first AC driven power, the second AC driven power and the 3rd AC driven power, and the first exchange drives
Power supply is used to drive microelectrode 310 to provide alternating potential for first fluid, and the second AC driven power is used to be the sample point
Alternating potential is provided from microelectrode 410, the 3rd AC driven power is that second fluid drives microelectrode 510 to provide alternation electricity
Gesture.And the friendship of first AC driven power, second AC driven power and the 3rd AC driven power output
The amplitude and frequency for becoming potential can adjust.In the embodiment of the present invention, it would however also be possible to employ the function signal generator of multichannel is made
It is AC driven power 600.
The application method of microfluidic separation device provided in an embodiment of the present invention can be：Assuming that mixing neutral corpuscle is two
Plant neutral corpuscle, respectively the first neutral corpuscle 710 and the second neutral corpuscle 720, and described two mixing neutral corpuscle freedom
It is distributed in the electrolyte solution that electrical conductivity is 0.001-0.085S/m, being respectively first fluid by function signal generator drives
Dynamic microelectrode 310, the sample separate microelectrode 410 and the second fluid drives microelectrode 510 to apply predeterminated frequency and pre-
If the sinusoidal alternating potential of amplitude, in containing two kinds of electrolyte solution input injection ports 210 of mixing neutral corpuscle, in first
Property the neutral corpuscle 720 of particulate 710 and second will with the flowing of electrolyte solution in chronological order successively reach outlet 220,
So as to realize the separation of different types of mixing neutral corpuscle.
As shown in figure 5, the embodiment of the present invention additionally provides a kind of microfluidic separation method, microfluidic separation dress is applied to
Put, to realize the separation of the mixing neutral corpuscle in electrolyte solution.The microfluidic separation device includes：First fluid drives
Micropump 300, separative element 400 and second fluid drive Micropump 500.Wherein, first fluid driving Micropump 300 includes first fluid
Driving microelectrode, separative element 400 includes that sample separates microelectrode, and second fluid drives Micropump 500 to be driven including second fluid
Microelectrode, and the first fluid drives microelectrode and the second fluid to drive microelectrode to be asymmetric electrode.It is described micro-
Stream control separation method includes：
S51：First fluid drives microelectrode to produce the first inhomogeneous field to drive first fluid to drive the electricity in Micropump
Electrolyte solution is with the first preset flow rate lateral flow to separative element；
S52：Sample separates microelectrode and produces the second inhomogeneous field by the mixing neutral corpuscle in separative element in longitudinal direction
Separated on direction；
S53：Second fluid drives microelectrode to produce the 3rd inhomogeneous field to flow into second fluid by separative element to drive
Drive Micropump in electrolyte solution in separate in a longitudinal direction mixing neutral corpuscle in various neutral corpuscles with
Second preset flow rate successively flows out in chronological order, wherein, second preset flow rate distribution gradient along the longitudinal direction.
Second fluid is driven in Micropump 500, in the variety classes that longitudinal direction, i.e., the z-axis direction shown in Fig. 4 are separated
Neutral corpuscle flowed with the second preset flow rate with electrolyte solution, because second preset flow rate is in z-axis direction
Gradient is distributed, for example first increases and then decreases along the z-axis direction, so that different types of neutral corpuscle that z-axis direction separates
Transverse flow speed of different sizes is obtained, so be gradually disengaged on horizontal direction, i.e., the x-axis direction shown in Fig. 4 come, finally
Second fluid will be successively flowed out in chronological order and drive Micropump 500, realize separating.
It is apparent to those skilled in the art that, for convenience and simplicity of description, the method for foregoing description
The corresponding course of work for implementing flow, may be referred in aforementioned means embodiment, will not be repeated here.
It should be noted that herein, such as first and second or the like relational terms are used merely to a reality
Body or operation make a distinction with another entity or operation, and not necessarily require or imply these entities or deposited between operating
In any this actual relation or order.And, term " including ", "comprising" or its any other variant be intended to
Nonexcludability is included, so that process, method, article or equipment including a series of key elements not only will including those
Element, but also other key elements including being not expressly set out, or also include being this process, method, article or equipment
Intrinsic key element.In the absence of more restrictions, the key element limited by sentence "including a ...", it is not excluded that
Also there is other identical element in process, method, article or equipment including the key element.
The preferred embodiments of the present invention are the foregoing is only, is not intended to limit the invention, for the skill of this area
For art personnel, the present invention can have various modifications and variations.It is all within the spirit and principles in the present invention, made any repair
Change, equivalent, improvement etc., should be included within the scope of the present invention.
Claims (10)
1. a kind of microfluidic separation device, for separating the mixing neutral corpuscle in electrolyte solution, it is characterised in that including：
First fluid drives Micropump, separative element and second fluid to drive Micropump；The first fluid driving Micropump includes first fluid
Driving microelectrode, the separative element includes that sample separates microelectrode, and the second fluid drives Micropump to be driven including second fluid
Dynamic microelectrode, the first fluid drives microelectrode and the second fluid to drive microelectrode to be asymmetric electrode；
The first fluid drives microelectrode for producing the first inhomogeneous field to drive the first fluid to drive in Micropump
Electrolyte solution with the first preset flow rate lateral flow to the separative element；
The sample separates microelectrode to be used to produce the second inhomogeneous field that the mixing neutral corpuscle in the separative element exists
Separated on longitudinal direction；
It is described by separative element inflow to drive that the second fluid drives microelectrode to be used for the 3rd inhomogeneous field of generation
Second fluid drive Micropump in electrolyte solution in separate in a longitudinal direction mixing neutral corpuscle in it is various in
Property particulate successively flowed out in chronological order with the second preset flow rate, wherein, second preset flow rate is along the longitudinal direction in gradient
Distribution.
2. microfluidic separation device according to claim 1, it is characterised in that also include：Cover plate and substrate, the cover plate
The microchannel formed on the substrate for electrolyte solution flowing is covered, the microchannel is first-class including what is be sequentially communicated
Body drives microchannel, separate microchannel and second fluid drives microchannel, and the first fluid drives microchannel to be located at described the
One fluid is driven in Micropump, and the separation microchannel is located in the separative element, and the second fluid drives microchannel to be located at
The second fluid is driven in Micropump, and the first fluid drives microelectrode, the sample to separate microelectrode and the second
Body drives microelectrode to be arranged on the first fluid with being corresponding in turn to and drives microchannel, the separation microchannel and the second
Body is driven on the substrate of microchannel bottom.
3. microfluidic separation device according to claim 2, it is characterised in that second preset flow rate is along the longitudinal direction
Distribution gradient is specially：With the increase away from second fluid driving microelectrode surface longitudinal distance, described second presets
Flow velocity first increases, and then reduces, and Gaussian Profile is presented.
4. the microfluidic separation device according to any one of claim 1-3, it is characterised in that the first fluid drives
Microelectrode and the second fluid drive microelectrode to be asymmetric interdigital parallel array electrode, and the asymmetric interdigital is put down
Row array electrode includes small electrode and large electrode, and the small electrode is in periodic distribution according to default spacing with the large electrode.
5. microfluidic separation device according to claim 4, it is characterised in that the sample separate microelectrode include it is interdigital
Formula parallel array electrode.
6. microfluidic separation device according to claim 1, it is characterised in that the first fluid drives the Micropump to include handing over
Stream electric osmose Micropump.
7. microfluidic separation device according to claim 1, it is characterised in that the first fluid drives the Micropump to include handing over
Stream electric heating Micropump.
8. microfluidic separation device according to claim 1, it is characterised in that the second fluid drives the Micropump to include handing over
Stream electric osmose Micropump.
9. microfluidic separation device according to claim 1, it is characterised in that also including AC driven power, the friendship
Stream driving power supply includes the first AC driven power, the second AC driven power and the 3rd AC driven power, and described first hands over
Stream driving power supply is used to drive microelectrode to provide alternating potential for the first fluid, and second AC driven power is for being
The sample separates microelectrode and provides alternating potential, and the 3rd AC driven power is that the second fluid drives microelectrode to carry
For alternating potential.
10. a kind of microfluidic separation method, is applied to microfluidic separation device, it is characterised in that the microfluidic separation device
Including：First fluid drives Micropump, separative element and second fluid to drive Micropump；The first fluid driving Micropump includes first
Fluid drives microelectrode, the separative element to separate microelectrode including sample, and the second fluid driving Micropump includes second
Body drives microelectrode, the first fluid to drive microelectrode and the second fluid to drive microelectrode to be asymmetric electrode；Institute
The method of stating includes：
The first fluid drives microelectrode to produce the first inhomogeneous field to drive the first fluid to drive the electricity in Micropump
Electrolyte solution is with the first preset flow rate lateral flow to the separative element；
The sample separates microelectrode and produces the second inhomogeneous field by the mixing neutral corpuscle in the separative element in longitudinal direction
Separated on direction；
The second fluid drives microelectrode to produce the 3rd inhomogeneous field to drive by separative element inflow described second
Fluid drives the various neutrality in the mixing neutral corpuscle for separating in a longitudinal direction in the electrolyte solution in Micropump micro-
Grain is successively flowed out in chronological order with the second preset flow rate, wherein, second preset flow rate distribution gradient along the longitudinal direction.
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| CN108355726B (en) * | 2018-01-08 | 2020-08-04 | 河北工业大学 | Interdigital type speed-increasing micropump chip based on alternating current thermal effect driving |
| CN110918139B (en) * | 2018-09-20 | 2023-09-29 | 上海欣戈赛生物科技有限公司 | Microfluidic chip, device containing microfluidic chip and sample concentration method |
| CN110601497B (en) * | 2019-09-05 | 2021-07-23 | 中国科学院力学研究所 | Alternating current electroosmosis driven ethanol traveling wave type micropump and working method |
| CN110601496B (en) * | 2019-09-05 | 2021-08-17 | 中国科学院力学研究所 | Alternating current electroosmosis driven ethanol asymmetric micropump and working method |
| CN112080392A (en) * | 2020-09-21 | 2020-12-15 | 长春理工大学 | Three-dimensional dielectrophoresis micro-fluidic chip for separating circulating tumor cells at high flux |
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