CN108977343A - The micro-fluidic chip separated for cell with capture based on dielectrophoresis principle - Google Patents
The micro-fluidic chip separated for cell with capture based on dielectrophoresis principle Download PDFInfo
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- CN108977343A CN108977343A CN201811030343.7A CN201811030343A CN108977343A CN 108977343 A CN108977343 A CN 108977343A CN 201811030343 A CN201811030343 A CN 201811030343A CN 108977343 A CN108977343 A CN 108977343A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/16—Microfluidic devices; Capillary tubes
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/02—Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
Abstract
The micro-fluidic chip separated for cell with capture based on dielectrophoresis principle, belong to microfluidic art, solves the problems, such as existing cell analysis work inefficiency due to cell sorting link takes a long time and cell sorting link is with the unicellular noncontinuity for capturing link.Separating for cell based on dielectrophoresis principle of the present invention applies electric field to the cell mixture in Disengagement zone by inclined driving electrode array with the micro-fluidic chip captured, different cells are sorted using the difference of dielectric property between different cells, and based on positive dielectrophoretic force and negative dielectrophoretic force.After completing cell sorting, separating with the micro-fluidic chip of capture realizing unicellular capture in such a way that bipolar electrode array is arranged in trapping region for cell based on dielectrophoresis principle of the present invention.
Description
Technical field
The present invention relates to a kind of micro-fluidic chips, belong to microfluidic art.
Background technique
Cell sorting and unicellular capture are necessary pre-treatment links in cell analysis work.Existing cell sorting side
Formula mainly includes fluorescence-activated cell sorting and the sorting of magnetic field active cell, however, either fluorescence-activated cell sorting, still
The sorting of magnetic field active cell, is required to implement many and diverse sample handling procedure.For example, before carrying out fluorescence-activated cell sorting
It needs to carry out fluorescent marker to cell, needs to carry out magnetic mark to cell before carrying out the sorting of magnetic field active cell.Therefore,
Existing cell sorting mode takes a long time, and seriously reduces the efficiency of cell analysis work.
On the other hand, existing cell sorting needs to realize by corresponding laboratory apparatus respectively with unicellular capture, by
This increases the cell transfer link after cell sorting, this also reduces the efficiency of cell analysis work to a certain extent.
Micro-fluidic chip (Micro fluidic Chip) is also known as chip lab (Lab-on-A-Chip), refers to handle
The basic operation units such as sample preparation involved in the fields such as biological and chemical, reaction, separation and detection integrate or baseset
At on the chip to one piece several square centimeters (even more small), network is formed by microchannel, analytic process is automatically performed, has sent out
It transforms into and is led for the very research with application prospect of the multi-crossed disciplines such as a machinery, chemistry, biology, medicine and hydrodynamics
Domain.
Summary of the invention
The present invention is to solve existing cell analysis work because cell sorting link takes a long time and cell sorting link
With the unicellular noncontinuity for capturing link the problem of inefficiency, propose it is a kind of based on dielectrophoresis principle for cell
The micro-fluidic chip of separation and capture.
Separating with the micro-fluidic chip captured for cell based on dielectrophoresis principle of the present invention includes glass base
Bottom 1, PDMS cover plate 2, driving electrode array 3 and first bipolar electrode array 4~third bipolar electrode array 6；
Invagination is provided with first runner 7~the 9th runner 15, Disengagement zone 16, first catches on the lower surface of PDMS cover plate 2
It obtains area's 17~third trapping region 19, first and flows into 20~third of groove inflow groove 22 and first outflow 23~third of groove outflow
Groove 25；
First flow into 20~third of groove flow into groove 22 respectively with inflow port~third flow channel 9 of first runner 7
Port is flowed into be connected, the outflow port of outflow port~third flow channel 9 of first runner 7 with the inflow port that separates 16th area
It is connected, the outflow port of Disengagement zone 16 is connected with inflow port~the 6th runner 12 inflow port of the 4th runner 10 simultaneously
It is logical, the outflow port of outflow six runner 12 of port~the of the 4th runner 10 inflow port~the with the first trapping region 17 respectively
The inflow port of three trapping regions 19 is connected, outflow port~third trapping region 19 outflow port difference of the first trapping region 17
It is connected with inflow port~the 9th runner 15 inflow port of the 7th runner 13, outflow port~9th of the 7th runner 13
The outflow port of runner 15 is connected with first outflow 23~third of groove outflow groove 25 respectively；
The first inflow through-hole is respectively arranged on the slot bottom that slot bottom~third of the first inflow groove 20 flows into groove 22
~third flows into through-hole, is respectively arranged on slot bottom~third outflow groove 25 slot bottom of the first outflow groove 23 first-class
Through-hole~third flows out through-hole out, and the first inflow through-hole~third flows into through-hole and the first outflow through-hole~third outflow through-hole is equal
Through PDMS cover plate 2；
In the outflow for flowing into port and the first outflow through-hole for flowing into port~third and flowing into through-hole that first flows into through-hole
Port~third outflow through-hole is respectively arranged with the first metal connector~the 6th metal connector on outflow port；
Driving electrode array 3 and first bipolar electrode array 4~third bipolar electrode array 6 are arranged at glass base
On the upper surface at bottom 1, the upper surface of substrate of glass 1 is opposite with the lower surface of PDMS cover plate 2 and fits closely；
Driving electrode array includes the 26~the 8th driving electrodes 33 of the first driving electrodes, and the first driving electrodes 26 and the 8th are driven
Moving electrode 33, the second driving electrodes 27 and the 7th driving electrodes 32, third driving electrodes 28 and the 6th driving electrodes 31 and the 4th
Driving electrodes 29 and the 5th driving electrodes 30 respectively constitute the first splayed structure~the 4th splayed structure, the first splayed knot
Structure~the 4th splayed structure successively and is in one row distributed in the inflow port of the outflow port and Disengagement zone 16 of Disengagement zone 16
Between, the small open side of small open side~the 4th splayed structure of the first splayed structure is towards the outflow end of Disengagement zone 16
Mouthful and with the inflow port face of the 5th runner 11, both ends~the 4th splayed of the big opening side of the first splayed structure
The both ends of the big opening side of structure exceed the two sides of Disengagement zone 16 respectively；
The both ends of the big opening side at the both ends and third splayed structure of the big opening side of the first splayed structure connect friendship
The both ends of galvanic electricity pressure, the big opening side at the both ends and the 4th splayed structure of the big opening side of the second splayed structure are grounded；
First bipolar electrode array 4~third bipolar electrode array 6 is located at first 17~third of trapping region and catches
In the coverage area for obtaining area 19；
First metal connector~third metal connector be respectively cell mixture, buffer solution and cell mixture into
Enter the channel of the micro-fluidic chip；
The dielectric constant for two kinds of cells that cell mixture is included is different.
As preferably, the structure of the 26~the 8th driving electrodes 33 of the first driving electrodes is identical, the first splayed structure
The small open side of small open side~the 4th splayed structure extended distance it is equal.
As preferably, each splayed structure passes through lead electrode 34 and is connected with voltage source or power ground.
As preferably, the structure of first bipolar electrode array 4~third bipolar electrode array 6 is identical, is
Wireless bipolar electrode array；
First bipolar electrode array 4 includes the 35~the 12nd driving electrodes 38 of the 9th driving electrodes and bipolar electrode battle array
Column ontology 39；
The both ends of 9th driving electrodes 35~the 12nd driving electrodes 38 both ends are applied with alternating voltage；
For the 35~the 12nd driving electrodes 38 of the 9th driving electrodes, the phase angle of the former both end voltage and the latter both ends electricity
90 ° of the carrier phase shift of pressure；
After connecing electricity, the 35~the 12nd driving electrodes 38 of the 9th driving electrodes are provided commonly for driving bipolar electrode array ontology
39。
As preferably, on the lower surface of PDMS cover plate 2 also invagination be provided with the tenth runner~the 15th runner and
First auxiliary flute~the 6th auxiliary flute；
First auxiliary flute and the second auxiliary flute pass through the tenth runner and the 11st runner and the first trapping region 17 respectively
It is connected, third auxiliary flute and the 4th auxiliary flute pass through the 12nd runner and the 13rd runner and the second trapping region 18 respectively
It is connected, the 5th auxiliary flute and the 6th auxiliary flute pass through the 14th runner and the 15th runner and third trapping region 19 respectively
It is connected.
As preferably, Disengagement zone 16 is rectangle, and the width for flowing into port and flowing out port of Disengagement zone 16 is impartial
Width in Disengagement zone 16；
The length L and width W of Disengagement zone 16 are respectively 4000 μm and 1400 μm；
The width W of the outflow port of first runner 7i1The outflow port W of~third flow channel 9i3Width be respectively 500 μm,
400 μm and 500 μm；
The width W of the inflow port of 4th runner 10o1The width W of the inflow port of~the six runner 12o3Respectively 550 μ
M, 300 μm and 550 μm；
The minimum spacing L of the outflow port of the small open side and Disengagement zone 16 of first splayed structuredIt is 300 μm.
As preferably, bipolar electrode array ontology 39 is square, the driving of the 9th driving electrodes the 35~the 12nd
The equal length of electrode 38 is 1400 μm；
The 35~the 12nd driving electrodes 38 of 9th driving electrodes are distributed in bipolar electrode array ontology along clockwise direction
Around 39, and it is parallel with the four edges of bipolar electrode array ontology 39 respectively；
The 35~the 12nd driving electrodes 38 of 9th driving electrodes and the minimum spacing of bipolar electrode array ontology 39 are homogeneous
Deng；
The minimum spacing G of 9th driving electrodes 35 and the 11st driving electrodes 37 is 2000 μm.
As preferably, first flows into 20~third of groove inflow groove 22, first trapping region 17~third trapping region
19, first outflow 23~third of groove outflow groove 25 and the first auxiliary flute~the 6th auxiliary flute are that round and diameter is equal
It is 5000 μm.
As preferably, the height in the invagination region of PDMS cover plate 2 is 20 μm.
As preferably, electrode involved in the micro-fluidic chip is ito thin film electrode or metal film electrode.
It is of the present invention that the micro-fluidic chip with capture is separated for cell based on dielectrophoresis principle, by separating
Driving electrode array 3 is arranged to realize the cell sorting to cell mixture, by catching in first 17~third of trapping region in area 16
It obtains area 19 and first bipolar electrode array 4~third bipolar electrode array 6 is respectively set to realize unicellular capture link.
Wherein, the basic principle of cell sorting are as follows:
A part of cell mixture successively flows into through-hole through the first metal connector, first, first flows into groove 20 and the
One runner 7 enters Disengagement zone 16, and buffer solution successively flows into through-hole, the second inflow groove 21 through the second metal connector, second
With second flow channel 8 enter Disengagement zone 16, another part cell mixture successively through third metal connector, third flow into through-hole,
Third flows into groove 22 and third flow channel 9 enters Disengagement zone 16.
The both ends of the big opening side at the both ends and third splayed structure of the big opening side of the first splayed structure connect friendship
The both ends of galvanic electricity pressure, the big opening side at the both ends and the 4th splayed structure of the big opening side of the second splayed structure are grounded.
Adjust the both ends of the both ends of the big opening side of the first splayed structure and the big opening side of third splayed structure
The amplitude and frequency of alternating voltage make two kinds of cells respectively by positive dielectrophoresis attraction and negative dielectrophoresis repulsive force.It will buffer molten
Movement speed and the movement of the cell by negative dielectrophoresis repulsive force by the cell of positive dielectrophoresis attraction is arranged in the flow velocity of liquid
Between speed.The cell that movement speed is greater than buffer solution flow velocity will be moved along inclined driving electrode array 3, and finally be passed through
5th runner 11 leaves Disengagement zone 16.The cell that movement speed is less than buffer solution flow velocity will enter the 4th stream with buffer solution
Road 10 and the 6th runner 12.
Separating for cell based on dielectrophoresis principle of the present invention is based on dielectrophoresis with the micro-fluidic chip captured
Principle realizes the sorting of cell.Compared with existing fluorescence-activated cell sorting and magnetic field active cell sort, of the invention is thin
Born of the same parents sort mode it is not necessary that cell is marked in advance, and time-consuming is relatively short, improve the efficiency of cell analysis work.Another party
Face, it is of the present invention based on dielectrophoresis principle for cell separate with capture micro-fluidic chip will sorting link with it is slender
Born of the same parents capture link and integrate, and the cell after eliminating cell sorting shifts link, this is also improved carefully to a certain extent
The efficiency of born of the same parents' analysis work.
Detailed description of the invention
Hereinafter it is used for based on the embodiments and with reference to the accompanying drawings carefully to of the present invention based on dielectrophoresis principle
Born of the same parents' separation and the micro-fluidic chip of capture are described in more detail, in which:
Fig. 1 is the structure separated for cell with the micro-fluidic chip captured described in embodiment based on dielectrophoresis principle
Perspective view；
Fig. 2 is the structural schematic diagram for the Disengagement zone that embodiment refers to；
Fig. 3 is the structural schematic diagram for the first bipolar electrode array that embodiment refers to, wherein LeFor the 9th driving electrodes
35 length；
Fig. 4 is that Clausius-Mosso of yeast cell and PS microballoon that embodiment refers to proposes the factor with electric voltage frequency
Variation relation figure, wherein void-PS microballoon curve, real-PS microballoon curve, void-saccharomycete curve and reality-saccharomycete curve difference
For PS microballoon Clausius-Mosso propose factor imaginary part, Clausius-Mosso of PS microballoon mentions factor real part, yeast cell
Clausius-Mosso propose factor imaginary part and Clausius-Mosso of yeast cell mentions factor real part with the change of electric voltage frequency
Change curve；
Fig. 5 be the first splayed structure that embodiment refers to and third splayed structure apply amplitude be 20Vpp, frequency
For the voltage of 1MHz, buffer solution flow velocity is the experiment separation process figure of the yeast cell and PS microballoon under 0.1mm/s；
Fig. 6 Fig. 5 after 10 seconds that has been the superposition that refers to of embodiment；
Fig. 7 is that the diameter for the single bipolar electrode that embodiment refers to is 25 μm, the gap of two neighboring bipolar electrode
It is 50 μm, applying alive frequency is 500KHz, and when amplitude is 10Vpp, bipolar electrode array ontology 39 is to single saccharomycete
The capture lab diagram of cell；
Fig. 8 is the flow chart for the PDMS passageway machining that embodiment refers to, wherein a is silicon base, and b is photoresist, and c is stream
Road template, d are the mixture of PDMS and curing agent, and UV is ultraviolet light；
Fig. 9 is the flow chart for the ito thin film electrode machining that embodiment refers to, e is ito thin film, and f is electrode template；
Figure 10 is the bond graph of embodiment the PDMS cover plate referred to and ITO substrate.
Specific embodiment
Below in conjunction with attached drawing to the miniflow of the present invention that separated for cell with capture based on dielectrophoresis principle
Control chip is described further.
Embodiment: the present embodiment is explained in detail below with reference to Fig. 1~Figure 10.
Separating with the micro-fluidic chip captured for cell based on dielectrophoresis principle includes glass described in the present embodiment
Substrate 1, PDMS cover plate 2, driving electrode array 3 and first bipolar electrode array 4~third bipolar electrode array 6；
Invagination is provided with first runner 7~the 9th runner 15, Disengagement zone 16, first catches on the lower surface of PDMS cover plate 2
It obtains area's 17~third trapping region 19, first and flows into 20~third of groove inflow groove 22 and first outflow 23~third of groove outflow
Groove 25；
First flow into 20~third of groove flow into groove 22 respectively with inflow port~third flow channel 9 of first runner 7
Port is flowed into be connected, the outflow port of outflow port~third flow channel 9 of first runner 7 with the inflow port that separates 16th area
It is connected, the outflow port of Disengagement zone 16 is connected with inflow port~the 6th runner 12 inflow port of the 4th runner 10 simultaneously
It is logical, the outflow port of outflow six runner 12 of port~the of the 4th runner 10 inflow port~the with the first trapping region 17 respectively
The inflow port of three trapping regions 19 is connected, outflow port~third trapping region 19 outflow port difference of the first trapping region 17
It is connected with inflow port~the 9th runner 15 inflow port of the 7th runner 13, outflow port~9th of the 7th runner 13
The outflow port of runner 15 is connected with first outflow 23~third of groove outflow groove 25 respectively；
The first inflow through-hole is respectively arranged on the slot bottom that slot bottom~third of the first inflow groove 20 flows into groove 22
~third flows into through-hole, is respectively arranged on slot bottom~third outflow groove 25 slot bottom of the first outflow groove 23 first-class
Through-hole~third flows out through-hole out, and the first inflow through-hole~third flows into through-hole and the first outflow through-hole~third outflow through-hole is equal
Through PDMS cover plate 2；
In the outflow for flowing into port and the first outflow through-hole for flowing into port~third and flowing into through-hole that first flows into through-hole
Port~third outflow through-hole is respectively arranged with the first metal connector~the 6th metal connector on outflow port；
Driving electrode array 3 and first bipolar electrode array 4~third bipolar electrode array 6 are arranged at glass base
On the upper surface at bottom 1, the upper surface of substrate of glass 1 is opposite with the lower surface of PDMS cover plate 2 and fits closely；
Driving electrode array includes the 26~the 8th driving electrodes 33 of the first driving electrodes, and the first driving electrodes 26 and the 8th are driven
Moving electrode 33, the second driving electrodes 27 and the 7th driving electrodes 32, third driving electrodes 28 and the 6th driving electrodes 31 and the 4th
Driving electrodes 29 and the 5th driving electrodes 30 respectively constitute the first splayed structure~the 4th splayed structure, the first splayed knot
Structure~the 4th splayed structure successively and is in one row distributed in the inflow port of the outflow port and Disengagement zone 16 of Disengagement zone 16
Between, the small open side of small open side~the 4th splayed structure of the first splayed structure is towards the outflow end of Disengagement zone 16
Mouthful and with the inflow port face of the 5th runner 11, both ends~the 4th splayed of the big opening side of the first splayed structure
The both ends of the big opening side of structure exceed the two sides of Disengagement zone 16 respectively；
The both ends of the big opening side at the both ends and third splayed structure of the big opening side of the first splayed structure connect friendship
The both ends of galvanic electricity pressure, the big opening side at the both ends and the 4th splayed structure of the big opening side of the second splayed structure are grounded；
First bipolar electrode array 4~third bipolar electrode array 6 is located at first 17~third of trapping region and catches
In the coverage area for obtaining area 19；
First metal connector~third metal connector be respectively cell mixture, buffer solution and cell mixture into
Enter the channel of the micro-fluidic chip；
The dielectric constant for two kinds of cells that cell mixture is included is different.
The structure of the 26~the 8th driving electrodes 33 of first driving electrodes of the present embodiment is identical, the first splayed structure it is small
The extended distance of the small open side of open side~the 4th splayed structure is equal.
Each splayed structure of the present embodiment passes through lead electrode 34 and is connected with voltage source or power ground.
The structure of first bipolar electrode array 4~third bipolar electrode array 6 of the present embodiment is identical, is wireless
Bipolar electrode array；
First bipolar electrode array 4 includes the 35~the 12nd driving electrodes 38 of the 9th driving electrodes and bipolar electrode battle array
Column ontology 39；
The both ends of 9th driving electrodes 35~the 12nd driving electrodes 38 both ends are applied with alternating voltage；
For the 35~the 12nd driving electrodes 38 of the 9th driving electrodes, the phase angle of the former both end voltage and the latter both ends electricity
90 ° of the carrier phase shift of pressure；
After connecing electricity, the 35~the 12nd driving electrodes 38 of the 9th driving electrodes are provided commonly for driving bipolar electrode array ontology
39。
Also invagination is provided with the tenth runner~the 15th runner and first auxiliary on the lower surface of the PDMS cover plate 2 of the present embodiment
Help groove~the 6th auxiliary flute；
First auxiliary flute and the second auxiliary flute pass through the tenth runner and the 11st runner and the first trapping region 17 respectively
It is connected, third auxiliary flute and the 4th auxiliary flute pass through the 12nd runner and the 13rd runner and the second trapping region 18 respectively
It is connected, the 5th auxiliary flute and the 6th auxiliary flute pass through the 14th runner and the 15th runner and third trapping region 19 respectively
It is connected.
The Disengagement zone 16 of the present embodiment is rectangle, and the inflows port of Disengagement zone 16 and the width for flowing out port are equal to point
Width from area 16；
The length L and width W of Disengagement zone 16 are respectively 4000 μm and 1400 μm；
The width W of the outflow port of first runner 7i1The outflow port W of~third flow channel 9i3Width be respectively 500 μm,
400 μm and 500 μm；
The width W of the inflow port of 4th runner 10o1The width W of the inflow port of~the six runner 12o3Respectively 550 μ
M, 300 μm and 550 μm；
The minimum spacing L of the outflow port of the small open side and Disengagement zone 16 of first splayed structuredIt is 300 μm.
The bipolar electrode array ontology 39 of the present embodiment is square, the 35~the 12nd driving electrodes of the 9th driving electrodes
38 equal length is 1400 μm；
The 35~the 12nd driving electrodes 38 of 9th driving electrodes are distributed in bipolar electrode array ontology along clockwise direction
Around 39, and it is parallel with the four edges of bipolar electrode array ontology 39 respectively；
The 35~the 12nd driving electrodes 38 of 9th driving electrodes and the minimum spacing of bipolar electrode array ontology 39 are homogeneous
Deng；
The minimum spacing G of 9th driving electrodes 35 and the 11st driving electrodes 37 is 2000 μm.
The present embodiment first flow into 20~third of groove flow into groove 22, first 17~third of trapping region trapping region 19,
First outflow 23~third of groove outflow groove 25 and the first auxiliary flute~the 6th auxiliary flute are that round and diameter is
5000μm。
The height in the invagination region of the PDMS cover plate 2 of the present embodiment is 20 μm.
It is used for involved in the micro-fluidic chip that cell is separated and captured described in the present embodiment based on dielectrophoresis principle
Electrode is ito thin film electrode or metal film electrode.
Below using the mixed liquor being made of yeast cell and PS microballoon as objective for implementation, it is described in detail described in the present embodiment
Based on dielectrophoresis principle for cell separate with capture micro-fluidic chip working principle:
Cell sorting part:
After applying electric field, act on particle when equal dielectrophoretic force expression formula are as follows:
ε*=ε-j (σ/ω) (3)
In formula, < FD> to act on the when equal dielectrophoretic force on particle, r is particle radius, and K (w) is Clausius-Mosso
The factor is proposed, Re [K (w)] and Im [K (w)] are respectively the real and imaginary parts that Clausius-Mosso proposes the factor, and E is electric field strength, wave
Unrestrained line is complex amplitude, and * is conjugate complex number；
WithThe respectively complex dielectric permittivity of particle and buffer solution；
ε is dielectric constant, and σ is conductivity.
By formula 1 it is found that dielectrophoretic force depends on the heterogeneity and K (w) of electric field.The first item of formula 1 is to pass
Unite dielectrophoretic force, when Re [K (w)] is positive perhaps negative particle will by positive dielectrophoretic force or negative dielectrophoretic force so that
Grain is attracted or far from strong electric field region.The Section 2 of formula 1 is traveling wave dielectrophoresis (twDEP), be positive as Im [K (w)] or
When person is negative, particle will increase or reduce direction along electric field phase and move.
Fig. 4 proposes the factor with the variation relation figure of electric voltage frequency for Clausius-Mosso of yeast cell and PS microballoon.Root
According to Fig. 4 it is found that when electric voltage frequency is within the scope of 100kHz-40MHz, yeast cell by positive dielectrophoretic force, PS microballoon by
Negative dielectrophoretic force.
It is learnt by experiment, when the amplitude of voltage is 10V, and frequency is greater than 1MHz, PS microballoon is 0.1S/m in conductivity
Buffer solution in negative dielectrophoresis to repel speed be about 0.17mm/s, yeast cell is molten in the buffering that conductivity is 0.1S/m
It is about 0.03mm/s that positive dielectrophoresis in liquid, which attracts speed,.Therefore, when buffer solution flow velocity is 0.04mm/s to 0.16mm/s,
Since the movement speed of PS microballoon is greater than the flow velocity of buffer solution, PS microballoon will be moved along inclined driving electrode array 3, and
Finally Disengagement zone 16 is left through the 5th runner 11.And since the movement speed of yeast cell is less than the flow velocity of buffer solution, ferment
Female bacterium cell will enter the 4th runner 10 and the 6th runner 12 with buffer solution.
Fig. 5 is that the first splayed structure and third splayed structure apply the electricity that amplitude is 20Vpp, frequency is 1MHz
Pressure, buffer solution flow velocity are the separation process figure of the yeast cell and PS microballoon under 0.1mm/s.Fig. 6 is after being superimposed 10 seconds
Fig. 5.According to Fig. 5 with Fig. 6 it is found that separating for cell based on dielectrophoresis principle and the miniflow of capture described in the present embodiment
Control chip can efficiently separate yeast cell and the realization of PS microballoon.
The instruction sheet cell capture part by taking the first bipolar electrode array 4 as an example: bipolar electrode refer to one not and outside
The conductor immersed between anode and cathode in electrolyte that power supply is connected.Bipolar electrode is placed in microfluidic channel, application is worked as
After certain driving DC potential, a potential drop will form in solution.Bipolar electrode is an equipotentiality body, and potential above is
It is identical, it will form an overpotential on bipolar electrode and solution interface in this way.Electric double layer is at the both ends of bipolar electrode
It is formed, when the overpotential on bipolar electrode is sufficiently large, electrochemical reaction will occur.Characteristic based on bipolar electrode,
The electrochemistry array of multiple wireless bipolar electrodes is designed between two driving electrodes, two driving electrodes can drive each
Electrochemical reaction occurs for a bipolar electrode.When application driving voltage be a high frequency ac signal rather than direct current telecommunications
Number when (frequency of electric field be higher than redox reaction in electronics transfer rate when), electrochemical reaction will be suppressed, bipolar
Capacitor charge and discharge effect will occur for the electric double layer at property electrode both ends.The electric field strength at bipolar electrode edge will be maximum, bipolar
The electric field strength of property electrode intermediate region will be minimum.Thus, the array that bipolar electrode is not only suitable for carrying out large-scale wireless is set
Meter, and the distribution of electric field can be adjusted by changing the size of bipolar electrode.
In the first bipolar electrode array 4 of the present embodiment, the 35~the 12nd driving electrodes 38 of the 9th driving electrodes are used for
Apply rotating electric field around bipolar electrode array ontology 39, and then utilizes negative dielectrophoretic force by cell capture to field strength energy
Measure low region.With it is existing using positive dielectrophoretic force by cell capture to the unicellular acquisition mode in the high region of field strength energy
It compares, the unicellular acquisition mode of the present embodiment is due to by cell capture to field strength energy low region to the adverse effect of cell
It is smaller, be conducive to subsequent cell analysis work.
Fig. 7 is that the diameter of single bipolar electrode is 25 μm, and the gap of two neighboring bipolar electrode is 50 μm, applies electricity
The frequency of pressure is 500KHz, and when amplitude is 10Vpp, bipolar electrode array ontology 39 tests the capture of single yeast cell
Figure.It is calculated according to experimental data, the capture rate of single yeast cell is up to 75%.Therefore, described in the present embodiment based on
Separating for cell for dielectrophoresis principle can be to unicellular carry out efficient capture with the micro-fluidic chip captured.
The preparation side separated for cell with the micro-fluidic chip captured described in the present embodiment based on dielectrophoresis principle
Method follows the steps below:
One, PDMS passageway machining:
(1), silicon base is cleaned: firstly, hand-washing silicon base using cleaning agent.Secondly, by silicon base be sequentially placed into acetone and
It is cleaned by ultrasonic respectively in isopropanol 10 minutes.Again, silicon base is rinsed using plasma water, and uses and is dried with nitrogen.Finally, will
Silicon base after drying is placed in baking box, 80 DEG C at a temperature of, heat 15 minutes.
(2), the tiling of photoresist: firstly, coating a layer photoresist in the upper surface of silicon base.Secondly, silicon base is put
It sets and is rotated on photoresist spinner with the speed of 1500r/s, up to photoresist is with a thickness of 100 microns.Finally, before being carried out to silicon base
It dries, silicon base is placed on 60 DEG C of hot plate, hot plate is heated to 95 DEG C, with temperature heating silicon base 1 hour.The light
Photoresist is the negative photoresist of 2050 model of SU-8.
(3), it exposes: firstly, runner template is placed in photoetching glue surface.Secondly, using light-transmitting plate by runner template with
Photoresist face pressure is tight.Finally, being exposed using quartz burner to it.
(4), develop: firstly, being dried after being carried out to the silicon base after exposure, silicon base being placed on 60 DEG C of hot plate, it will
Hot plate was heated to 95 DEG C, with temperature heating silicon base 35 minutes.Secondly, silicon base after cooling is placed in SU-8 developer solution
Middle development 10 minutes.Again, plasma water cleaning carried out to silicon base, be dried with nitrogen.Finally, silicon base is placed in baking box
In, 80 DEG C at a temperature of, heat 10 minutes to 20 minutes, obtain PDMS runner mould.
(5), PDMS is poured: firstly, PDMS is mixed with curing agent with the mass ratio of 10:1, and using clean glass
Glass stick stirs 15 minutes to 20 minutes, is uniformly mixed it.Secondly, being taken out using mixture of the vacuum pump to PDMS and curing agent true
It is 30 minutes empty, to eliminate the bubble in mixture.Again, silanization treatment is carried out to PDMS runner mould, makes PDMS runner mould
The surface of son deposits one layer of silane.Finally, the mixture of PDMS and curing agent is poured on the silane face of PDMS runner mould, and
It is vacuumized 20 minutes using vacuum pump, to eliminate the bubble in mixture, 80 DEG C at a temperature of, heat 2 hours, make it
Solidification.
The silylation layer on the surface of PDMS runner mould is for avoiding PDMS runner mould and the mixture adhesion.
(6), the channel PDMS is handled: firstly, the PDMS after solidification is slowly taken off from PDMS runner mould.Secondly, adopting
The shape to match with substrate of glass is cut into blade.Finally, using Slot digger and punch, to the PDMS after solidification
Grooving and punching are carried out, PDMS cover plate 2 is obtained.
Fig. 8 is the flow chart of PDMS passageway machining.
Two, the processing of ito thin film electrode:
(1), clean ITO substrate: ITO substrate includes substrate of glass 1 and ito thin film, the cleaning method and silicon substrate of ITO substrate
The cleaning method at bottom is identical.
(2), the tiling of photoresist: firstly, coating a layer photoresist on ito thin film.Secondly, ITO substrate is placed on
It is rotated 40 seconds on photoresist spinner with the speed of 3100r/s.Finally, carrying out soft baking to ITO substrate, ITO substrate is placed on 100 DEG C
On hot plate, heat 6 minutes.
The photoresist is the photoresist of AZ4620 model.
(3), it exposes: ITO substrate being placed under quartz burner and is exposed.
(4), develop: the ITO substrate after exposure is placed in AZ developer solution, develop 4 minutes to 5 minutes.
(5), corrode ito thin film: the ITO substrate after development being placed in the hydrochloric acid solution that mass ratio is 60%, and be added
Iron chloride impregnates 40 minutes, corrodes to ito thin film as catalyst.During this, exposed cured photoresist layer is risen
The effect of protection ito thin film is arrived, the ito thin film of photoresist overlay is not corroded.
(6), it removes photoresist: after the corrosion for completing ito thin film, ITO substrate being placed in the NaOH solution that mass ratio is 5%
Middle immersion removes cured photoresist, obtains ito thin film electrode.
Fig. 9 is the flow chart of ito thin film electrode machining.
Three, PDMS cover plate 2 and ITO substrate are bonded
Firstly, being arranged PDMS cover plate 2 in ITO substrate, and place it in the chamber of plasma machine, according to it is equal from
The use step of handset carries out plasma processing, makes PDMS cover plate 2 and ITO substrate sealed set, constitutes micro-fluidic chip.
Secondly, taking out micro-fluidic chip, and under the microscope, the relative position of the internal structure of micro-fluidic chip is carried out
Calibration.
Finally, firmly press a few minutes after completing calibration, be then placed in baking box, under conditions of 80 DEG C, heating
30 minutes, obtain micro-fluidic chip.
Figure 10 is the bond graph of PDMS cover plate 2 Yu ITO substrate.
Although describing the present invention herein with reference to specific embodiment, it should be understood that, these realities
Applying example only is the example of principles and applications.It should therefore be understood that can be permitted exemplary embodiment
More modifications, and can be designed that other arrangements, without departing from spirit of the invention as defined in the appended claims and
Range.It should be understood that different appurtenances can be combined by being different from mode described in original claim
It is required that and feature described herein.It will also be appreciated that the feature in conjunction with described in separate embodiments can be used at it
In his embodiment.
Claims (10)
1. the micro-fluidic chip separated for cell with capture based on dielectrophoresis principle, which is characterized in that the micro-fluidic core
Piece includes that substrate of glass (1), PDMS cover plate (2), driving electrode array (3) and the first bipolar electrode array (4)~third are double
Polar electric pole array (6)；
Invagination is provided with first runner (7)~the 9th runner (15), Disengagement zone (16), the on the lower surface of PDMS cover plate (2)
One trapping region (17)~third trapping region (19), first flow into groove (20)~third and flow into groove (22) and the first outflow groove
(23)~third outflow groove (25)；
First flow into groove (20)~third flow into groove (22) respectively with inflow port~third flow channel of first runner (7)
(9) inflow port is connected, outflow port~third flow channel (9) outflow port of first runner (7) with separate (16)
The inflow port in area is connected, the outflow port of Disengagement zone (16) while inflow port~the 6th runner with the 4th runner (10)
(12) inflow port is connected, and outflow port~the 6th runner (12) outflow port of the 4th runner (10) is respectively with first
The inflow port of trapping region (17)~third trapping region (19) inflow port is connected, the outflow port of the first trapping region (17)
The outflow port of~third trapping region (19) respectively with the inflow port of the 7th runner (13)~the 9th runner (15) inflow end
Mouth is connected, and groove (23) are flowed out with first respectively in outflow port~the 9th runner (15) outflow port of the 7th runner (13)
~third outflow groove (25) is connected；
The first inflow through-hole is respectively arranged on the slot bottom that slot bottom~third that first flows into groove (20) flows into groove (22)
~third flows into through-hole, is respectively arranged with the on slot bottom~third outflow groove (25) slot bottom of the first outflow groove (23)
One outflow through-hole~third flows out through-hole, and the first inflow through-hole~third flows into through-hole and the first outflow through-hole~third outflow is logical
Kong Jun runs through PDMS cover plate (2)；
In the outflow port for flowing into port and the first outflow through-hole for flowing into port~third and flowing into through-hole that first flows into through-hole
The first metal connector~the 6th metal connector is respectively arranged on the outflow port of~third outflow through-hole；
Driving electrode array (3) and the first bipolar electrode array (4)~third bipolar electrode array (6) are arranged at glass
On the upper surface of substrate (1), the upper surface of substrate of glass (1) is opposite with the lower surface of PDMS cover plate (2) and fits closely；
Driving electrode array includes the first driving electrodes (26)~the 8th driving electrodes (33), the first driving electrodes (26) and the 8th
Driving electrodes (33), the second driving electrodes (27) and the 7th driving electrodes (32), third driving electrodes (28) and the 6th driving electricity
Pole (31) and the 4th driving electrodes (29) and the 5th driving electrodes (30) respectively constitute the first splayed structure~the 4th splayed
Structure, the first splayed structure~the 4th splayed structure successively and be in one row distributed in the outflow port of Disengagement zone (16) with
Between the inflow port of Disengagement zone (16), the small open side of small open side~the 4th splayed structure of the first splayed structure is equal
Outflow port towards Disengagement zone (16) and inflow port face with the 5th runner (11), the first splayed structure it is big
The both ends of the both ends of open side~the 4th splayed structure big opening side exceed the two sides of Disengagement zone (16) respectively；
The both ends of the big opening side at the both ends and third splayed structure of the big opening side of the first splayed structure connect alternating current
Pressure, the both ends of the big opening side at the both ends and the 4th splayed structure of the big opening side of the second splayed structure are grounded；
First bipolar electrode array (4)~third bipolar electrode array (6) is located at the first trapping region (17)~third
In the coverage area of trapping region (19)；
First metal connector~third metal connector is respectively that cell mixture, buffer solution and cell mixture enter institute
State the channel of micro-fluidic chip；
The dielectric constant for two kinds of cells that cell mixture is included is different.
2. separating the micro-fluidic chip with capture, feature for cell based on dielectrophoresis principle as described in claim 1
It is, the structure of the first driving electrodes (26)~the 8th driving electrodes (33) is identical, the small open side of the first splayed structure~
The extended distance of the small open side of 4th splayed structure is equal.
3. separating the micro-fluidic chip with capture, feature for cell based on dielectrophoresis principle as claimed in claim 2
It is, each splayed structure passes through lead electrode (34) and is connected with voltage source or power ground.
4. separating the micro-fluidic chip with capture, feature for cell based on dielectrophoresis principle as claimed in claim 3
It is, the first bipolar electrode array (4)~third bipolar electrode array (6) structure is identical, is wireless bipolarity electricity
Pole array；
First bipolar electrode array (4) includes the 9th driving electrodes (35)~the 12nd driving electrodes (38) and bipolar electrode
Array ontology (39)；
The both ends of 9th driving electrodes (35)~the 12nd driving electrodes (38) both ends are applied with alternating voltage；
For the 9th driving electrodes (35)~the 12nd driving electrodes (38), the phase angle of the former both end voltage and the latter both ends electricity
90 ° of the carrier phase shift of pressure；
After connecing electricity, the 9th driving electrodes (35)~the 12nd driving electrodes (38) are provided commonly for driving bipolar electrode array ontology
(39)。
5. separating the micro-fluidic chip with capture, feature for cell based on dielectrophoresis principle as claimed in claim 4
Be, on the lower surface of PDMS cover plate (2) also invagination be provided with the tenth runner~the 15th runner and the first auxiliary flute~
6th auxiliary flute；
First auxiliary flute and the second auxiliary flute pass through the tenth runner and the 11st runner and the first trapping region (17) phase respectively
Connection, third auxiliary flute and the 4th auxiliary flute pass through the 12nd runner and the 13rd runner and the second trapping region (18) respectively
It is connected, the 5th auxiliary flute and the 6th auxiliary flute pass through the 14th runner and the 15th runner and third trapping region respectively
(19) it is connected.
6. separating the micro-fluidic chip with capture, feature for cell based on dielectrophoresis principle as claimed in claim 5
It is, Disengagement zone (16) are rectangle, and the inflow port of Disengagement zone (16) and the width of outflow port are equal to Disengagement zone (16)
Width；
The length L and width W of Disengagement zone (16) are respectively 4000 μm and 1400 μm；
The width W of the outflow port of first runner (7)i1The outflow port W of~third flow channel (9)i3Width be respectively 500 μm,
400 μm and 500 μm；
The width W of the inflow port of 4th runner (10)o1The width W of the inflow port of~the six runner (12)o3Respectively 550 μ
M, 300 μm and 550 μm；
The minimum spacing L of the outflow port of the small open side and Disengagement zone (16) of first splayed structuredIt is 300 μm.
7. separating the micro-fluidic chip with capture, feature for cell based on dielectrophoresis principle as claimed in claim 6
It is, bipolar electrode array ontology (39) is square, the length of the 9th driving electrodes (35)~the 12nd driving electrodes (38)
It spends equal, is 1400 μm；
9th driving electrodes (35)~the 12nd driving electrodes (38) are distributed in bipolar electrode array ontology along clockwise direction
(39) around, and it is parallel with the four edges of bipolar electrode array ontology (39) respectively；
9th driving electrodes (35)~the 12nd driving electrodes (38) and the minimum spacing of bipolar electrode array ontology (39) are equal
It is equal；
The minimum spacing G of 9th driving electrodes (35) and the 11st driving electrodes (37) is 2000 μm.
8. separating the micro-fluidic chip with capture, feature for cell based on dielectrophoresis principle as claimed in claim 7
It is, first, which flows into groove (20)~third, flows into groove (22), the first trapping region (17)~third trapping region (19), first-class
Groove (23)~third outflow groove (25) and the first auxiliary flute~the 6th auxiliary flute are that round and diameter is out
5000μm。
9. separating the micro-fluidic chip with capture, feature for cell based on dielectrophoresis principle as claimed in claim 8
It is, the height in the invagination region of PDMS cover plate (2) is 20 μm.
10. separating the micro-fluidic chip with capture, feature for cell based on dielectrophoresis principle as claimed in claim 9
It is, electrode involved in the micro-fluidic chip is ito thin film electrode or metal film electrode.
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|---|---|---|---|---|
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Citations (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006058245A2 (en) * | 2004-11-29 | 2006-06-01 | The Regents Of The University Of California | Dielectrophoretic particle sorter |
| CN101250483A (en) * | 2008-04-11 | 2008-08-27 | 重庆大学 | Combined splint microelectrode type micro-fluidic dielectrophoresis cell separation and enrichment chip |
| WO2009008925A2 (en) * | 2007-04-05 | 2009-01-15 | The Regents Of The University Of California | A particle-based microfluidic device for providing high magnetic field gradients |
| KR20090083655A (en) * | 2008-01-30 | 2009-08-04 | 인제대학교 산학협력단 | Dielectrophoretic microseparator |
| CN101745438A (en) * | 2010-01-19 | 2010-06-23 | 东南大学 | Method for carrying out streaming counting sort by utilizing micro light pattern |
| WO2012165711A1 (en) * | 2011-06-02 | 2012-12-06 | 연세대학교 산학협력단 | High efficiency particle separating apparatus and method |
| CN103732731A (en) * | 2011-05-27 | 2014-04-16 | 不列颠哥伦比亚大学 | Microfluidic cell trap and assay apparatus for high-throughput analysis |
| CN103889556A (en) * | 2011-01-06 | 2014-06-25 | Gpb科学有限责任公司 | Circulating tumor cell capture on a microfluidic chip incorporating both affinity and size |
| US20140251813A1 (en) * | 2013-03-08 | 2014-09-11 | Cfd Research Corporation | Bipolar electrode sample preparation devices |
| CN104136907A (en) * | 2011-12-07 | 2014-11-05 | Imec公司 | Analysis and sorting of objects in flow |
| CN105233891A (en) * | 2015-10-21 | 2016-01-13 | 哈尔滨工业大学 | Micro-fluidic chip used for capturing and rotating micro-size particles and preparation method and application of micro-fluidic chip |
| US20160299138A1 (en) * | 2015-04-10 | 2016-10-13 | The Curators Of The University Of Missouri | High Sensitivity Impedance Sensor |
| CN106399091A (en) * | 2016-09-13 | 2017-02-15 | 哈尔滨工业大学 | Cell capturing chip based on inductive charge electro-osmosis induced by rotating electric field |
| CN106497786A (en) * | 2016-11-18 | 2017-03-15 | 清华大学深圳研究生院 | A kind of for unicellular seizure and culture micro-fluidic chip |
| CN106824318A (en) * | 2017-03-29 | 2017-06-13 | 哈尔滨工业大学 | A kind of minute yardstick particle separating chips based on induced charge electric osmose and dielectrophoresis and preparation method and application |
| CN106918627A (en) * | 2017-04-26 | 2017-07-04 | 淮阴工学院 | A kind of analysis and detection device based on closed bipolar electrode array |
-
2018
- 2018-09-04 CN CN201811030343.7A patent/CN108977343B/en active Active
Patent Citations (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006058245A2 (en) * | 2004-11-29 | 2006-06-01 | The Regents Of The University Of California | Dielectrophoretic particle sorter |
| WO2009008925A2 (en) * | 2007-04-05 | 2009-01-15 | The Regents Of The University Of California | A particle-based microfluidic device for providing high magnetic field gradients |
| KR20090083655A (en) * | 2008-01-30 | 2009-08-04 | 인제대학교 산학협력단 | Dielectrophoretic microseparator |
| CN101250483A (en) * | 2008-04-11 | 2008-08-27 | 重庆大学 | Combined splint microelectrode type micro-fluidic dielectrophoresis cell separation and enrichment chip |
| CN101745438A (en) * | 2010-01-19 | 2010-06-23 | 东南大学 | Method for carrying out streaming counting sort by utilizing micro light pattern |
| CN103889556A (en) * | 2011-01-06 | 2014-06-25 | Gpb科学有限责任公司 | Circulating tumor cell capture on a microfluidic chip incorporating both affinity and size |
| CN103732731A (en) * | 2011-05-27 | 2014-04-16 | 不列颠哥伦比亚大学 | Microfluidic cell trap and assay apparatus for high-throughput analysis |
| WO2012165711A1 (en) * | 2011-06-02 | 2012-12-06 | 연세대학교 산학협력단 | High efficiency particle separating apparatus and method |
| CN104136907A (en) * | 2011-12-07 | 2014-11-05 | Imec公司 | Analysis and sorting of objects in flow |
| US20140251813A1 (en) * | 2013-03-08 | 2014-09-11 | Cfd Research Corporation | Bipolar electrode sample preparation devices |
| US20160299138A1 (en) * | 2015-04-10 | 2016-10-13 | The Curators Of The University Of Missouri | High Sensitivity Impedance Sensor |
| CN105233891A (en) * | 2015-10-21 | 2016-01-13 | 哈尔滨工业大学 | Micro-fluidic chip used for capturing and rotating micro-size particles and preparation method and application of micro-fluidic chip |
| CN106399091A (en) * | 2016-09-13 | 2017-02-15 | 哈尔滨工业大学 | Cell capturing chip based on inductive charge electro-osmosis induced by rotating electric field |
| CN106497786A (en) * | 2016-11-18 | 2017-03-15 | 清华大学深圳研究生院 | A kind of for unicellular seizure and culture micro-fluidic chip |
| CN106824318A (en) * | 2017-03-29 | 2017-06-13 | 哈尔滨工业大学 | A kind of minute yardstick particle separating chips based on induced charge electric osmose and dielectrophoresis and preparation method and application |
| CN106918627A (en) * | 2017-04-26 | 2017-07-04 | 淮阴工学院 | A kind of analysis and detection device based on closed bipolar electrode array |
Non-Patent Citations (5)
| Title |
|---|
| BASHAR YAFOUZ 等: "The Design and Simulation of a Planar Microarray Dot Electrode for a Dielectrophoretic Lab-on-Chip Device", 《INTERNATIONAL JOURNAL OF ELECTROCHEMICAL SCIENCE》 * |
| XIAOYUAN HU 等: "Marker-specific sorting of rare cells", 《PNAS》 * |
| YUPAN WU 等: "High-Throughput Separation, Trapping, and Manipulation of Single Cells and Particles by Combined Dielectrophoresis at a Bipolar Electrode Array", 《ANALYTICAL CHEMISTRY》 * |
| 吴菲: "集成单细胞捕获的微流控细胞分选芯片研究", 《中国优秀博硕士学位论文全文数据库(硕士)信息科技辑》 * |
| 黄笛 等: "基于微流控技术的循环肿瘤细胞分选研究", 《化学进展》 * |
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|---|---|---|---|---|
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| CN110004043A (en) * | 2019-04-09 | 2019-07-12 | 东北大学 | A kind of unicellular capture micro-fluidic chip |
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| CN112034029B (en) * | 2020-09-11 | 2022-12-20 | 华南师范大学 | Microfluid dielectrophoresis separation device and manufacturing method thereof |
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Inventor after: Ren Yukun Inventor after: Jiang Tianyi Inventor after: Wu Yupan Inventor after: Jiang Hongyuan Inventor before: Jiang Hongyuan Inventor before: Ren Yukun Inventor before: Wu Yupan |
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