CN109967150A - It is a kind of for manipulating the inertia micro-fluidic chip of micro-nano granules - Google Patents
It is a kind of for manipulating the inertia micro-fluidic chip of micro-nano granules Download PDFInfo
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- CN109967150A CN109967150A CN201910334273.2A CN201910334273A CN109967150A CN 109967150 A CN109967150 A CN 109967150A CN 201910334273 A CN201910334273 A CN 201910334273A CN 109967150 A CN109967150 A CN 109967150A
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Abstract
The invention discloses a kind of for manipulating the inertia micro-fluidic chip of micro-nano granules, and inertia micro-fluidic chip includes upper substrate and underlying basal；There are inlet opening, upper half entrance liquid storage pool, upper half inertia runner, upper half outlet liquid storage pool and fluid hole, inlet opening and fluid hole to be connected with the external world on upper substrate；Underlying basal is equipped with lower half entrance liquid storage pool, lower half inertia runner and lower half and exports liquid storage pool；Upper half entrance liquid storage pool is superimposed with lower half entrance liquid storage pool and is assembled to form entrance liquid storage pool, and upper half inertia runner and the trace-stacking of lower half inertia flow are assembled to form inertia runner, and upper half outlet liquid storage pool and lower half outlet liquid storage pool superposition are assembled to form outlet liquid storage pool；Inlet opening is successively connected with entrance liquid storage pool, inertia runner, outlet liquid storage pool, fluid hole；The width of flow path of inertia runner is greater than runner height；Inertia runner space structure is the curved runner of stepped cross section.This chip volume is small, manipulation precision is good, flux is high and simple for production.
Description
Technical field
The present invention relates to a kind of for manipulating the inertia micro-fluidic chip of micro-nano granules, belongs to micro-fluidic field, can use
It captures, focus and separates in the accurate manipulation application of micro-nano biologic grain, such as the accurate of micro-nano biological cell.
Background technique
Portable instant detector device is commented in the diagnosis of reply scene burst acute illness, malignant disease early screening and prognosis
Estimate, push personalized medicine development etc. has significant application value, is the important carrier towards people's livelihood health demand, in recent years
Carry out the great attention by department, national governments.As the key technology of instant detector device, micro-fluidic chip has detection speed
The advantages such as degree is fast, high sensitivity, at low cost, integration is good, suit the technical need detected immediately, have become the neck at present very much
The research hotspot in domain.
It is one extremely heavy in instant detection pretreatment link that biological cell, which accurately manipulates and (such as captures, focuses and separate),
The committed step wanted directly determines the sensitivity and reliability of subsequent detection result to sample treatment efficiency and precision.Mirror
In this, domestic and foreign scholars have carried out a large amount of exploratory development for the cell control method based on microflow control technique, it was recently reported that one
Manipulation technology (i.e. active manipulation, such as dielectrophoresis, magnetophoresis, sound tweezer, optical tweezer of the series based on physical fields such as electricity, magnetic, sound, light
Deng), (i.e. passive type manipulates, and such as certainty lateral displacement, is used at micro- barrier filtering for manipulation technology based on fluid channel self structure
Property is micro-fluidic etc.), and based on active and the manipulation technology passively mixed.The Real time and controllable of active manipulation is good, but sample
Processing flux is lower and operating process is more complex；And passive type manipulation processing flux it is higher and be not necessarily to additional physical field, therefore
There is preferably integrated advantage in miniaturized devices.
Wherein, inertia microflow control technique is acted on migration in fact by inertia force in runner using effect of fluid inertia inducing cell
Now accurate manipulation, there is flow passage structure to be simple and convenient to operate, manipulate the advantages such as precision height, the extensive pass by domestic and foreign scholars
Note.However, effect of fluid inertia has strong dependency to cell apparent size, it is difficult to the cell of high concentration and adjoining dimensions into
The accurate manipulation (such as separate and capture the circulating tumor cell in blood) of row, and the accurate acquisition of such cell is for some great
Diagnosis, monitoring and the great application for the treatment of of disease and scientific value.
Therefore, conventional inertia microflow control technique is broken through, the handling of micro-nano biologic grain is promoted, expands inertia miniflow
Raw doctor's application range of control will provide Research foundation for the early screening of major disease and prognosis treatment, realize that inertia is micro- to be final
The industrial application of fluidic chip provides technical support.
Summary of the invention
Goal of the invention: in order to overcome the shortcomings of the prior art, the present invention provides a kind of for manipulating micro-nano granules
Inertia micro-fluidic chip, the chip volume is small, without sheath fluid, manipulation precision is good, flux is high, can satisfy micro-nano biology
The accurate manipulation application of grain.
To achieve the above object, the technical solution adopted by the present invention are as follows:
Of the invention is a kind of for manipulating the inertia micro-fluidic chip of micro-nano granules, including upper substrate and lower layer's base
Piece；The upper substrate is equipped with inlet opening, upper half entrance liquid storage pool, upper half inertia runner, upper half and exports liquid storage pool and out liquid
Hole, the inlet opening and fluid hole are connected with the external world, import and export for micro-nano particle solution；The underlying basal
It is equipped with lower half entrance liquid storage pool, lower half inertia runner and lower half and exports liquid storage pool；The upper half entrance liquid storage pool enters with lower half
Mouth liquid storage pool superposition is assembled to form entrance liquid storage pool, and the upper half inertia runner and the trace-stacking of lower half inertia flow are assembled to form inertia
Runner, the upper half outlet liquid storage pool and lower half outlet liquid storage pool superposition are assembled to form outlet liquid storage pool；The inlet opening is successively
It is connected with entrance liquid storage pool, inertia runner, outlet liquid storage pool, fluid hole；The width of flow path of the inertia runner is greater than runner
Highly, for enhancing the inertia effect of micro-nano granules in inertia runner；The space structure of the inertia runner is stepped horizontal
The curved runner in section generates the asymmetric quadratic equation eddying field effect perpendicular to section main flow direction, enhancing for making in inertia runner
The inertia of micro-nano granules migrates ability of regulation and control；The horizontal relative position of the upper substrate and underlying basal is adjustable, makes institute
The cross-sectional shape and size for stating inertia runner change, for regulate and control the shape of asymmetric quadratic equation eddying field, direction, size and
Position.
Micro-nano granules size relationship in above-mentioned inertia runner cross sectional dimensions and runner are as follows:
a/DH< 0.07, a/Dh>=0.07, wherein a is the diameter of micro-nano granules, DHFor the outer of inertia flow channel cross-section
Wall face height, DhFor the inner wall height of inertia flow channel cross-section.
It is above-mentioned stepped including L shape or Z-shaped.
Above-mentioned curved runner is spiral of Archimedes structure or periodic sinusoidal wave structure.
Above-mentioned inertia micro-fluidic chip for realizing two or more different size micro-nano granules inertial separation, and two kinds
The size difference of micro-nano granules is within 5 μm.
The material of above-mentioned inertia micro-fluidic chip is dimethyl silicone polymer, thermoplastic polymer, glass or silica gel.
It is had the beneficial effect that caused by the present invention:
Inertia micro-fluidic chip proposed by the present invention breaches the micro-fluidic general runner structural model of conventional inertia, design
The curved runner chip of novel stepped cross-sections structure (such as L shape and Z-shaped section), makes in curved runner perpendicular to section master
Asymmetric secondary vortex flow effect is produced on flow direction；Change stepped cross-sections and curved flow passage structure size, i.e., by changing
Shape, direction, intensity and the position for becoming asymmetric secondary flow vortices can make micro-nano in any position in curved flow channel cross-section
Secondary Flow drag force suffered by particle changes.
Due to the inertia lift effect that micro-nano granules are also induced by wall surface in curved runner, by micro-nano granules
Suffered Secondary Flow drag force is coupled with inertia lift, and the resultant force by adjusting Secondary Flow drag force and inertia lift can be into
Step refining and the inertia performance of control for promoting micro-nano granules can be obviously improved the inertia manipulation precision of micro-nano granules,
Solves the skill that the micro-fluidic middle symmetrical secondary stream effect of conventional inertia is faced in terms of adjoining dimensions particle is precisely separated manipulation
Art bottleneck problem.
Chip volume of the invention is small, be not necessarily to sheath fluid, manipulation precision is good, flux is high and simple for production, in micro-nano granules
Focusing, capture, the separation of (such as biological cell) have potential using value in terms of accurately manipulating.
Detailed description of the invention
Fig. 1 is the 3D structural schematic diagram of inertia micro-fluidic chip；
Fig. 2 is the layered substrates 3D structural schematic diagram of inertia micro-fluidic chip；
Fig. 3 is the L shape cross section of fluid channel structural schematic diagram of inertia micro-fluidic chip；
Fig. 4 is the Z-shaped cross section of fluid channel structural schematic diagram of inertia micro-fluidic chip；
Fig. 5 is the helical flow path structure schematic diagram of inertia micro-fluidic chip；
Fig. 6 is the periodic sinusoidal wave current road structural schematic diagram of inertia micro-fluidic chip；
Fig. 7 is micro-nano biologic grain separating experiment platform schematic diagram；
Fig. 8 is random distribution schematic diagram of the micro-nano biologic grain in Z-shaped cross section and spiral flow channel inlet；
Fig. 9 is the simulation model figure of asymmetric quadratic equation eddying field in Z-shaped cross section and spiral flow channel；
Figure 10 is inertial separation schematic diagram of the micro-nano granules in helical flow path exit；
Figure 11 is the simulation model figure in Dien flow field in traditional rectangular cross section and spiral flow channel；
Wherein, 1 is upper substrate, and 2 be underlying basal, and 3 be inlet opening, 4 is entrance liquid storage pool, 5 is inertia runner, 6 is
Outlet liquid storage pool, 7 be fluid hole, 41 be upper half entrance liquid storage pool, 42 be lower half entrance liquid storage pool, 51 be upper half inertia runner,
52 be lower half inertia runner, 61 be upper half outlet liquid storage pool, 62 be lower half outlet liquid storage pool.
Specific embodiment
Preferred embodiment of the present invention will be described with reference to the accompanying drawing, it should be understood that preferred reality described herein
Apply example only for the purpose of illustrating and explaining the present invention and is not intended to limit the present invention.
As shown in Figure 1, 2, inertia micro-fluidic chip proposed by the present invention is made of upper substrate 1 and underlying basal 2, including
Inlet opening 3, entrance liquid storage pool 4, inertia runner 5, outlet liquid storage pool 6 and the fluid hole 7 being sequentially communicated.Upper substrate 1 includes upper
Half entrance liquid storage pool 41, upper half inertia runner 51, upper half outlet liquid storage pool 61, inlet opening 3 and fluid hole 7, and inlet opening 3 and go out
Fluid apertures 7 is connected with the external world, imports and exports for micro-nano particle solution；Underlying basal 2 includes lower half entrance liquid storage pool
42, lower half inertia runner 52 and lower half export liquid storage pool 62.The quantity for exporting liquid storage pool 6 and fluid hole 7 is two.
As shown in Figure 3,4, the lower half inertia runner 52 of the upper half inertia runner 51 of upper substrate 1 and underlying basal 2 is superimposed
It is assembled together to form L shape cross section or Z-shaped cross section, changes the horizontal relative position of two layers of substrate, can effectively adjust
The geomery of cross section.
As shown in Figure 5,6, the inertia runner 5 of inertia micro-fluidic chip is curved runner, and curved runner can be Archimedes's spiral shell
Spiral line structure is also possible to periodic sinusoidal wave structure.To make the micro-nano granules in inertia runner 5 generate sufficiently strong inertia
Effect, inertia runner 5 need to have aspect ratio flow path features, i.e. width of flow path is greater than runner height.In addition, inertia runner 5
Cross sectional dimensions and runner in micro-nano granules size relationship need to meet such as lower inequality:
a/DH< 0.07, a/Dh>=0.07, wherein a is the diameter of micro-nano granules, DHFor the outer of inertia flow channel cross-section
Wall face height, DhFor the inner wall height of inertia flow channel cross-section.
In the present embodiment, the material of inertia micro-fluidic chip is medical grade PET plastic, and the strength of materials is good, translucidus is high,
And there is good bio-compatibility, it is a kind of preferred material of inexpensive micro-fluidic chip.Micro-fluidic chip uses micro- injection molding
Processing technology made, all micro-structures in chip two layers of substrate can pass through precise injection molding one-pass molding.Substrate production
After the completion, two layers of substrate is put into positioning tool, assembles and is aligned all micro-structures.Using hot melting process to two layers of substrate into
Row hot pressing, makes substrate surface melt and be bonded together since temperature raises, completes the accurate encapsulation of chip.Using above-mentioned micro- note
Modeling technique can realize the high-volume production of micro-fluidic chip.
As shown in fig. 7, the inertia micro-fluidic chip in the present embodiment can be used for accurate point of different size micro-nano granules
From application.By taking the inertia runner 5 of L shape cross section spiral of Archimedes structure as an example, pumped two kinds not using precise injection
Micron particles solution with size injects micro-fluidic chip (Fig. 7 experiment porch) with certain flow, micron particles solution pass through into
Fluid apertures 3 is entered in inertia runner 5 by entrance liquid storage pool 4.It is influenced by the flow-disturbing of microfluid in entrance liquid storage pool 4, micron particles are molten
Liquid is in random distribution state (Fig. 8) in the runner of inlet at the beginning.Since the cross section of inertia runner 5 is L shape, make miniflow
Body is and asymmetric perpendicular to the asymmetric secondary flow vortices for generating two opposite flowings in micron particles solution main flow direction
The flow field intensity of secondary flow vortices gradually enhances (Fig. 9 simulation result) from runner inner wall face toward runner outside wall surface direction, so that two
Secondary stream swirling action is in the Secondary Flow drag force F on micron particlesDAlso it correspondingly changes with the difference of sectional position,
I.e. the Secondary Flow drag force suffered by the micron particles at runner outside wall surface is greater than at runner inner wall face suffered by micron particles
Secondary Flow drag force.Due to micron particles in inertia runner 5 also by the inertia lift F from runner wall surfaceLEffect, therefore
Design the L shape cross-sectional shape of helical flow path 5 and the optimization structure of runner, the shape of adjustable asymmetric secondary flow vortices
Shape, direction, intensity and position.By Secondary Flow drag force suffered by accuracy controlling micron particles and inertia lift, to make not
Micron particles with size are by different Secondary Flow drag forces-inertia lift bonding force effect, i.e., small sized particles are by strong by two
Secondary stream drag force leading role is entrapped at the strong vortice of close runner outside wall surface, and large-size particle is by strong inertia lift master
The effect of leading focuses at runner inner wall face, so that realizes at runner exit two kinds of different sized particles is precisely separated (Figure 10).
As a comparison, the present embodiment emulates the fluid motion in traditional rectangular cross section and spiral flow channel, simulation model
As shown in figure 11.Since cross section of fluid channel is rectangle, so that microfluid is generating symmetrical parallel two two perpendicular to main flow direction
Secondary stream vortex, i.e. Dien stream effect.Since Dien stream is equal in the flow field intensity of runner vertical direction, so that Dien stream acts on
Secondary Flow drag caused by micro-nano granules lacks flexibility, and the inertia that can not further promote micro-nano granules focuses migration energy
Power, therefore traditional rectangular cross section and spiral flow channel is poor in the separation application aspect manipulation precision of reply adjoining dimensions biological cell.
And the L shape cross section helical flow path structure in the present embodiment is used, it can be generated in inertia runner 5 significant asymmetric secondary
Whirlpool effect is flowed, can be used for being precisely separated the biological cell of adjoining dimensions, the haemocyte and circulating tumor in such as separation blood are thin
Born of the same parents' (about 5 μm of size difference) are expected to provide technical support for the early screening of malignant tumour and prognosis diagnosis and treatment.
In conclusion the inertia micro-fluidic chip that the present embodiment proposes has accurate micro-nano granules inertia handling
Can, and without sheath fluid supply, compact, easy to operate, flux is high, can be used for micro-nano biological cell efficient capture, gather
The manipulation applications such as burnt and separation have extensive in terms of integrated microfluidic chip laboratory, portable instant detector
Application value.
The above is only a preferred embodiment of the present invention, it should be pointed out that: for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (6)
1. a kind of for manipulating the inertia micro-fluidic chip of micro-nano granules, it is characterised in that: including upper substrate (1) and lower layer
Substrate (2)；The upper substrate (1) be equipped with inlet opening (3), upper half entrance liquid storage pool (41), upper half inertia runner (51), on
Half outlet liquid storage pool (61) and fluid hole (7), the inlet opening (3) and fluid hole (7) are connected with the external world, for micro-nano
Particle solution imports and export；The underlying basal (2) be equipped with lower half entrance liquid storage pool (42), lower half inertia runner (52) and
Lower half exports liquid storage pool (62)；The upper half entrance liquid storage pool (41) is superimposed with lower half entrance liquid storage pool (42) is assembled to form entrance
Liquid storage pool (4), the upper half inertia runner (51) is superimposed with lower half inertia runner (52) to be assembled to form inertia runner (5), described
Upper half outlet liquid storage pool (61) and lower half outlet liquid storage pool (62) superposition are assembled to form outlet liquid storage pool (6)；The inlet opening (3)
Successively it is connected with entrance liquid storage pool (4), inertia runner (5), outlet liquid storage pool (6), fluid hole (7)；The inertia runner (5)
Width of flow path be greater than runner height, for enhancing the inertia effect of micro-nano granules in inertia runner (5)；The inertia runner
(5) space structure is the curved runner of stepped cross section, is generated in inertia runner (5) perpendicular to section main flow direction for making
Asymmetric quadratic equation eddying field effect, enhance micro-nano granules inertia migration ability of regulation and control；The upper substrate (1) and lower layer's base
The horizontal relative position of piece (2) is adjustable, so that the cross-sectional shape of the inertia runner (5) is changed with size, for adjusting
Control shape, direction, the size and location of asymmetric quadratic equation eddying field.
2. according to claim 1 for manipulating the inertia micro-fluidic chip of micro-nano granules, it is characterised in that: described used
Property runner (5) cross sectional dimensions and runner in micro-nano granules size relationship are as follows:
a/DH< 0.07, a/Dh>=0.07, wherein a is the diameter of micro-nano granules, DHFor the outside wall surface of inertia flow channel cross-section
Highly, DhFor the inner wall height of inertia flow channel cross-section.
3. according to claim 1 for manipulating the inertia micro-fluidic chip of micro-nano granules, it is characterised in that: the rank
Ladder type includes L shape or Z-shaped.
4. according to claim 1 for manipulating the inertia micro-fluidic chip of micro-nano granules, it is characterised in that: described curved
Runner is spiral of Archimedes structure or periodic sinusoidal wave structure.
5. according to claim 1 for manipulating the inertia micro-fluidic chip of micro-nano granules, it is characterised in that: described used
Property micro-fluidic chip can be used for realizing the inertial separations of two or more different size micro-nano granules, and two kinds of micro-nano granules
Size difference is within 5 μm.
6. according to claim 1 for manipulating the inertia micro-fluidic chip of micro-nano granules, it is characterised in that: described used
Property micro-fluidic chip material be dimethyl silicone polymer, thermoplastic polymer, glass or silica gel.
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| CN110465339A (en) * | 2019-09-03 | 2019-11-19 | 浙江大学 | A method of it flowing solid two-phase and transports middle particle positioning |
| CN110975775A (en) * | 2019-10-29 | 2020-04-10 | 肇庆市华师大光电产业研究院 | High-flux three-dimensional microfluid mixing device based on dean flow effect and mixing method thereof |
| CN110975948A (en) * | 2019-11-06 | 2020-04-10 | 佛山市铬维科技有限公司 | Micro-fluidic cell counter |
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| CN112547145A (en) * | 2020-11-19 | 2021-03-26 | 东南大学 | Rare cell rapid screening micro-fluidic device |
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| WO2022161373A1 (en) * | 2021-01-29 | 2022-08-04 | 广州万孚生物技术股份有限公司 | Biological particle sorting flow channel and microfluidic chip |
| CN112509724B (en) * | 2021-02-03 | 2021-04-27 | 之江实验室 | Method and device for supporting optical trap particles |
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| CN114534809A (en) * | 2022-02-25 | 2022-05-27 | 河海大学常州校区 | Microfluidic particle control device with adjustable cross section shape and particle control method |
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