CN108285869A - Surface acoustic wave through the optimization of special wellability sorts chip - Google Patents

Surface acoustic wave through the optimization of special wellability sorts chip Download PDF

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CN108285869A
CN108285869A CN201810209228.XA CN201810209228A CN108285869A CN 108285869 A CN108285869 A CN 108285869A CN 201810209228 A CN201810209228 A CN 201810209228A CN 108285869 A CN108285869 A CN 108285869A
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sorting
chip
wellability
surface acoustic
cell
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CN108285869B (en
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刘国君
何芳
李岩
赵虹
李新波
刘建芳
杨志刚
詹从红
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Jilin University
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    • C12MAPPARATUS 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • C12M23/16Microfluidic devices; Capillary tubes
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12M35/00Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/02Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04Cell isolation or sorting

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Abstract

The invention discloses the surface acoustic waves optimized through special wellability to sort chip.The chip blends the Partial Feature that wellability optimization, wideband/frequency conversion interdigital transducer technology, waterpower sort and surface acoustic wave method for separating, realizes and is sorted to cell/particle high throughput enrichment, specific cells/particle high-purity.When chip operation, surface acoustic wave that interdigital transducer generates in fluid channel fluid and cell/particle impose the effect of sound field and acoustic radiation force.In addition, because the substrate of sorting runner uses special wellability optimization processing, there will be the differences such as surface tension, adhesive force, shearing force and wall slippage in different wellability film micro areas interface.When being arranged in the cell of team by sorting region, cell will deviate from its primary flow line tracking under acoustic streaming effect, acoustic radiation force, viscous force (the Stokes power) the effects that, under the coupling that special wellability optimizes substrate, the migration velocity of cell/particle and apart from increase, improves sorting flux and efficiency.

Description

Surface acoustic wave through the optimization of special wellability sorts chip
Technical field:
The present invention relates to surface acoustic waves to sort chip, the more particularly to novel surface acoustic wave point through the optimization of special wellability Select chip.
Background technology:
Surface wettability is one of important feature of the surface of solids, usually carrys out table with contact angle (contact angle, CA) Levy the infiltration degree of liquid versus solid.In general, when the contact angle of the surface of solids and water is more than 90 °, referred to as hydrophobic surface; When less than 90 °, referred to as water-wetted surface.And when contact angle is more than 150 ° or close to 0 °, both extreme wellability surfaces claim Be super-hydrophobic and ultra-hydrophilic surface.Special wellability surface includes three classes:It is super hydrophilic/super-hydrophobic reversible transition, super hydrophilic-super Hydrophobic pattern surface and gradient wellability surface.Special wellability surface is in automatically cleaning, antifog, corrosion-resistant, grease point There is huge applications foreground from, the lossless transfer of liquid, liquid transporting, blood compatibility material etc..Surface wettability optimizes skill The wellability optimizing surface of art relative maturity, various forms and structure is also relatively easy to, sol-gel method, electricity Chemical method, method of electrostatic spinning, plasma technique, oxidation-reduction method, hydro-thermal method, phase separation method, vapour deposition process, layer by layer from The process for modifying surface such as construction from part, template obtain more commonly used.
In recent decades, micro-fluidic sorting technology has become one of medicine, bioengineering, pharmacy and chemical field Important Platform is especially suffered from cancer cell detection, medical diagnosis on disease, drug screening and histology engineering and is widely answered With.Have the research that many research teams are dedicated to micro-fluidic particle sorting technology, the sorting based on micro-fluidic chip at present Technology can be mainly divided into two major classes, be active sorting technology and passive sorting technology respectively.Wherein active sorting technology is main It is the difference made by application external fields of force in fluid channel including dielectrophoresis sorting, sound sorting, magnetic separation and light sorting etc. Suspended particles or cell are moved along different tracks, and then achieve the purpose that sorting.Passive sorting technology is mainly including inertia point Choosing, micro-structure filtering, certainty laterally offset, field flow and waterpower sorting, compatibility sorting etc., are to utilize some special constructions Or fluid makes the movement locus of different suspended particles or cell change the Stokes power that suspended particles generate, in turn Realize the sorting of suspended particles in fluid.Each sorting technology all has respective advantage and characteristic, usually, passive point Selecting technology has higher flux, and the manipulation of active sorting technology is more accurate, is more easy to realize high-precision sorting.
Micro-fluidic particle sorting technology based on surface acoustic wave (SAW) is a kind of emerging in recent years sorting technology.According to The difference of action principle, application of the surface acoustic wave in particle sorting are broadly divided into two classes:Surface acoustic wave standing wave sorts harmony table Surface wave traveling wave sorts.When the principle of surface acoustic wave standing wave sorting is the fluid in surface acoustic wave standing wave effect fluid channel, it is based on sound Effect is flowed, the pressure node and pressure anti-node of period profile can be formed in runner, suspended particles are under the action of acoustic radiation force It can migrate to pressure node or pressure anti-node, and then realize sorting;The principle of surface acoustic wave traveling wave sorting is surface acoustic wave list When direction acts on the fluid in fluid channel, the suspended particles of different attribute (density, diameter, compressible) are by acoustic radiation force It is of different sizes, therefore lateral migration distance is also different, and then realize sorting.
The two indices that flux and purity often mutually restrict in most of sorting technologies, flux rising then mean Purity declines, and vice versa.And the general flux of existing passive sorting technology is high but sharpness of separation is low, and active sorting technology one As sharpness of separation it is high but flux is low.
Invention content:
The purpose of the present invention is to solve the above problems, and provide the surface acoustic wave sorting optimized through special wellability Chip, the chip include piezoelectric substrate, wideband/frequency conversion interdigital transducer (IDT) in piezoelectric substrate and sorting flow passage system group At wherein sorting flow passage system has being similar to for low adhesive force by the sorting runner substrate and warp optimized through special wellability The PDMS runners composition of the modifying super hydrophobicity processing of " lotus leaf effect ".And after PDMS runners are using wellability optimization, it will improve and divide It selects chip to the removal of bubble and anti-interference ability and automatical cleaning ability, improves its job stability and reliability.
The surface acoustic wave sorting chip through the optimization of special wellability of the present invention can be used for sorting based on traveling wave surface acoustic wave The sorting chip of principle and the sorting chip based on standing wave surface acoustic wave grading principle.
The sorting runner substrate of sorting chip based on traveling wave surface acoustic wave grading principle uses super hydrophilic/super-hydrophobic interval Property dot pattern surface (1701) or use gradient wellability surface (1702).It will in different wellability film micro areas interface There are the differences such as surface tension, adhesive force, shearing force and wall slippage.When carrying out the sorting of cell/particle, acoustic streaming effect, Cell/particle will deviate from its primary flow line tracking under the effects that acoustic radiation force, viscous force (Stokes power), in special wellability Under the coupling for optimizing substrate, the function and effect for being similar to dustpan " sieve rice raises chaff " formula will be generated, increase the inclined of cell/particle Distance is moved, cell/particle sorting flux and the efficiency of separation are improved.
The sorting runner substrate of sorting chip based on standing wave surface acoustic wave grading principle is using super hydrophilic/super-hydrophobic equidistant Striped stride formula patterned surface and strip pattern (29) is parallel with pressure node line.Using super hydrophilic/super-hydrophobic equidistant strip Compartment patterned surface accelerates cell/particle to the movement speed of pressure node line, and the sorting for improving cell/particle is logical Amount and the efficiency of separation.
The technical solution adopted by the present invention is:
One layer of photoetching for carrying interdigital transducer pattern is drawn respectively on clean piezoelectric substrate surface using photoetching technique Glue makes interdigital transducer using sputtering+stripping technology on piezoelectric substrate surface.
Sort runner substrate surface be modified scheme, using sol-gal process, electrochemical process and LBL self-assembly technique come It realizes.Particular technique route prepares TiO2 films using above-mentioned technique in lithium niobate base on piece, then passes through molecular self-assembling skill Art selectively carries out ultraviolet light in one layer of silicon fluoride film layer of its surface-assembled using photomask, be finally completed it is super hydrophilic/ Super-hydrophobic pattern modification;
PDMS runners pass through the bowl structure surface modification treatment with low adhesive force, specifically use template, laser ablation Method is used as substrate first after silicon substrate prepares micron order rough surface, then is made with modified surface of casting method PDMS fluid channels.
PDMS fluid channels through over cleaning are bonded in the surface of piezoelectric substrate.
Advantage of the invention is that:Through special wellability optimization surface acoustic wave sorting chip special wellability is optimized, Wideband/frequency conversion interdigital transducer (IDT) technology, the Partial Feature of waterpower sorting and surface acoustic wave method for separating blend, and realize To cell/particle high throughput enrichment, specific cells/particle high-purity sorting.
Description of the drawings:
Fig. 1 is the isometric side view of the embodiment of the present invention 1.
Fig. 2 is the grading principle schematic diagram of the embodiment of the present invention 1.
Fig. 3 is the special wellability structural schematic diagram of sorting runner of the embodiment of the present invention 1.
Fig. 4 is the isometric side view of the embodiment of the present invention 2.
Fig. 5 is the grading principle schematic diagram of the embodiment of the present invention 2.
Fig. 6 is the surface-modification structures schematic diagram of the PDMS runners of the present invention.
Specific implementation mode:
The present invention proposes that the surface acoustic wave that optimize through special wellability sorts chip, which optimizes special wellability, Wideband/frequency conversion interdigital transducer (IDT) technology, the Partial Feature of waterpower sorting and surface acoustic wave method for separating blend, and can use In the sorting chip (such as embodiment 1) based on traveling wave surface acoustic wave grading principle and point based on standing wave surface acoustic wave grading principle Chip (such as embodiment 2) is selected, realizes that the high-purity of high-throughput enrichment and specific cells to cell/particle sorts.
The structure of the embodiment of the present invention 1 referring to Fig.1, Fig. 3 and Fig. 6:
Referring to Fig.1, the chip is mainly by piezoelectric substrate (2), the wideband belt interdigital transducer (3) of double trapezoid structure and micro- Flow passage system (1) forms, and wherein micro sprue system (1) includes that sheath fluid flows into interface (5) and (8), cell/particle flux incoming interface (7), sheath fluid flow into runner (4) and (9), cell/particle flux air stream enter runner (6), maxicell/particle outflow runner (11), it is medium carefully Born of the same parents/particle outflow runner (14), cellule/particle outflow runner (16), maxicell/particle outflow outlet (12), intermediate cell/ Particle outflow outlet (13), cellule/particle outflow outlet (15) and the sorting runner (10) optimized through special wellability.
Referring to Fig.1, Fig. 3 and Fig. 6, the sorting runner (10) through the optimization of special wellability is by using super hydrophilic/super-hydrophobic Every property dot pattern surface (1701) or using gradient wellability surface (1702) modified sorting runner substrate and warp The PDMS sorting runner compositions of modifying super hydrophobicity processing are crossed, and PDMS sorting water passage surface modified structures are with low adhesive force Bowl structure.
The grading principle of the embodiment of the present invention 1 is with reference to Fig. 2:
With reference to Fig. 2, the cell with different characteristics/particle mixed liquor is noted with certain flow by flowing into interface (7) Enter to sort in flow passage system.Sheath fluid is injected into sorting flow passage system by flowing into interface (5) and (8) respectively with certain flow In, wherein the flow of interface (8) is more than the flow of interface (5).(PBS is slow in both sides sheath fluid for cell to be sorted/particle mixed liquor Fliud flushing) constraint under, with spread pattern along sorting runner along to side wall (and not in contact with to avoid surface acoustic wave " corner imitate Answer ") it is moved with laminar flow.Double trapezoid structure interdigital transducer (IDT) (3) is arranged on the inside of chip, when work, the sound of generation Surface wave in fluid channel fluid and cell/particle impose the effect of sound field and acoustic radiation force.When the cell/grain for being arranged in team When son is by sorting region, acoustic streaming effect, acoustic radiation force, viscous force (the Stokes power) the effects that under cell/particle will be inclined From its primary flow line tracking, under the coupling of special wellability optimization substrate (17), it will generate and be similar to dustpan " sieve meter Yang The function and effect of chaff " formula.Bulky cell/population is vortexed by acoustic streaming and acoustic radiation force acts on bigger, will be sorted first Out, smaller cell/particle remains in sprue and is dragged to wall surface or apart from wall surface closer to place;In sprue downstream Place, flow velocity reduce, and recycle waterpower grading principle to carry out secondary sorting at this time, to realize cell/particle separation;
The structure and grading principle of the embodiment of the present invention 2 are with reference to Fig. 4, Fig. 5 and Fig. 6:
With reference to Fig. 4, the chip mainly by piezoelectric substrate (19), become the wide structure of finger frequency conversion interdigital transducer 20 (2001, 2002,2003,2004) and micro sprue system (18) composition, wherein micro sprue system (18) includes that cell/particle mixed liquor flows into Interface (21) sorts runner (22), maxicell/particle outflow runner (23), intermediate cell/particle outflow runner (26), is small thin Born of the same parents/particle outflow runner (28), maxicell/particle outflow outlet (24), intermediate cell/particle outflow outlet (25), cellule/ Particle outflow outlet (27).Chip is designed using two couples of IDT, a pair of to be arranged perpendicular to runner, and team is arranged in for cell;Separately A pair of of IDT and the angled arrangement of runner, the high-purity for specific cells sort.
Referring to figure 5 and figure 6, the Disengagement zone substrate of the sorting runner (22) of the chip uses super hydrophilic/super-hydrophobic equidistant item Shape compartment patterned surface (29), chip PDMS runners are handled using modifying super hydrophobicity, and PDMS water passage surface modified structures For the bowl structure with low adhesive force.
With reference to Fig. 6, the surface acoustic wave that IDT is generated forms pressure node and pressure antinode in microchannel.When work, carefully Born of the same parents/particle mixed liquor is arranged in team's processing by the completion of first standing-wave sound field, after sorting area into standing wave, cell will actively to Pressure node line is mobile and the migration of movement locus is carried out along pressure nodel line.And maxicell/particle is in standing-wave sound field, acoustic radiation force And it is more mobile to pressure node under super hydrophilic/super-hydrophobic equidistant striped stride formula pattern wellability substrate (29) coupling Soon, the initiative bigger that track migration is carried out along nodal line is separated to deviate original streamline at first, remaining is less than normal Cell/particle recycle waterpower separating method carry out secondary separation.

Claims (4)

1. the surface acoustic wave through the optimization of special wellability sorts chip, which is characterized in that including in piezoelectric substrate, piezoelectric substrate Wideband/frequency conversion interdigital transducer (IDT) and sorting flow passage system composition, wherein sorting flow passage system through special wellability by optimizing Sorting runner substrate and through modifying super hydrophobicity handle PDMS runners form.
2. the surface acoustic wave according to claim 1 through the optimization of special wellability sorts chip, which is characterized in that based on row The sorting runner substrate of the sorting chip of wave sound surface wave grading principle uses super hydrophilic/super-hydrophobic intermittent dot pattern table Face (1701) uses gradient wellability surface (1702).
3. the surface acoustic wave according to claim 1 through the optimization of special wellability sorts chip, which is characterized in that based on staying The sorting runner substrate of the sorting chip of wave sound surface wave grading principle uses super hydrophilic/super-hydrophobic equidistant striped stride formula pattern Change surface and strip pattern is parallel with pressure node line.
4. the surface acoustic wave according to claim 1 through the optimization of special wellability sorts chip, which is characterized in that PDMS flows Road is handled using the modifying super hydrophobicity with low adhesive force.
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109012775A (en) * 2018-10-09 2018-12-18 深圳亘流科技有限公司 General inertia focuses micro-fluidic chip
CN109868218A (en) * 2019-03-26 2019-06-11 西安交通大学 A kind of nanobacteria cracking reactor and bacteria lysis method based on surface acoustic wave
CN110468026A (en) * 2019-09-07 2019-11-19 桂林电子科技大学 A kind of micro flow chip for optical fiber light power cell operation
CN110468027A (en) * 2019-09-07 2019-11-19 桂林电子科技大学 A kind of cell sorting micro flow chip based on coaxial double wave guiding fiber
CN110591889A (en) * 2019-09-07 2019-12-20 桂林电子科技大学 Microfluidic chip cell sorter based on coaxial double-waveguide optical fiber
CN113134399A (en) * 2021-04-27 2021-07-20 吉林大学 Large-flux cell acoustic sorting chip
CN113996362A (en) * 2021-12-03 2022-02-01 郑州轻工业大学 Liquid drop fusion microfluidic device and method based on focusing acoustic surface regulation

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CN208167024U (en) * 2018-03-14 2018-11-30 吉林大学 The surface acoustic wave sorting chip optimized through special wellability
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JP2000165192A (en) * 1998-11-30 2000-06-16 Kyocera Corp Surface acoustic wave device
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Cited By (11)

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Publication number Priority date Publication date Assignee Title
CN109012775A (en) * 2018-10-09 2018-12-18 深圳亘流科技有限公司 General inertia focuses micro-fluidic chip
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CN109868218A (en) * 2019-03-26 2019-06-11 西安交通大学 A kind of nanobacteria cracking reactor and bacteria lysis method based on surface acoustic wave
CN110468026A (en) * 2019-09-07 2019-11-19 桂林电子科技大学 A kind of micro flow chip for optical fiber light power cell operation
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CN110591889B (en) * 2019-09-07 2022-05-17 桂林电子科技大学 Microfluidic chip cell sorter based on coaxial double waveguide fibers
CN113134399A (en) * 2021-04-27 2021-07-20 吉林大学 Large-flux cell acoustic sorting chip
CN113996362A (en) * 2021-12-03 2022-02-01 郑州轻工业大学 Liquid drop fusion microfluidic device and method based on focusing acoustic surface regulation
CN113996362B (en) * 2021-12-03 2023-02-03 郑州轻工业大学 Liquid drop fusion microfluidic device and method based on focusing surface acoustic wave regulation

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