CN109975265A - A kind of three-dimensional reducing and expansion micro-fluidic device and method of multidirectional induction Dean stream - Google Patents
A kind of three-dimensional reducing and expansion micro-fluidic device and method of multidirectional induction Dean stream Download PDFInfo
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
Abstract
The three-dimensional reducing and expansion micro-fluidic device and method of the multidirectional induction Dean stream of one kind of the invention, use suitable for tumor research field.It includes micro-fluidic chip, three-dimensional reducing and expansion runner is equipped in micro-fluidic chip, the head and the tail both ends of three-dimensional reducing and expansion runner be respectively equipped with the micro-fluidic chip external world together with inlet connector and Outlet connector, inlet connector be equipped with entry conductor, Outlet connector be equipped with delivery channel；Wherein it is the entrance of cylindrical space at three-dimensional reducing and expansion flow channel entry point connector, is the outlet of cylindrical space at Outlet connector, polycondensation-expansion structure is equipped between middle part and outlet, there are distances between polycondensation-expansion structure and outlet.Its structure is simple, overcomes the shortcomings of that the inertia micro-fluidic devices such as existing spiral, asymmetric sinusoidal and plane reducing and expansion are only capable of the inductive formation Dean in the transverse direction of section and are vortexed, the precision and sensitivity of flow cytometer detection is substantially improved.
Description
Technical field:
The invention patent relates to a kind of three-dimensional reducing and expansion micro-fluidic device and methods, are particularly suitable for a kind of tumor research field
In without used under the conditions of sheath liquid stream and outfield force multidirectional induction Dean stream three-dimensional reducing and expansion micro-fluidic device and method.
Background technique:
With the development of the times, malignant tumour has become the significant problem for influencing mankind's publilc health, and the people are to health
Contradiction between the pursuit of happy life scarcity opposite with medical diagnosis resource becomes increasingly conspicuous.Point of care diagnostic (Point-of-
Care testing, POCT) instrument, because having detection device micromation, operating process simplification, diagnostic result just-in-time and inspection
The unique advantages such as survey expense is popular are improving the construction of scarcity of resources regional healthcare, reply burst accident disaster and are pushing family
The fields such as nursing diagnosis have broad prospect of application, are to solve above-mentioned contradictory powerful.Rely on advanced micro-structure processing work
Skill, micro-fluidic (Microfluidic) technology accurately manipulate microlitre, milliliter rank sample by micron order runner, are exploitations new one
For the mainstream technology of POCT instrument.
As one of important pretreatment unit of POCT instrument, the prefocusing precision of sample will directly restrict the property of detecting instrument
It can index.Existing micro-fluidic focusing technology can be summarized as following three classes according to the difference of manipulation mechanism: the first kind is macro from tradition
The sheath fluid that sight method develops presss from both sides Flow Technique；Second class is the active focusing technology based on outfields such as electricity, magnetic, sound, light；Third
Class is to be based on complicated form fluid channel inducing fluid, and the passive focusing technology of particle is manipulated by fluid self-acting.To thin
Born of the same parents detection for, ideal particle focus device should include it is 1. easy to operate, 2. without sheath liquid stream assist, 3. focus a fluid stream it is narrow,
4. focal position is far from runner wall surface, the features such as 5. processing flux is high.Though scholars have obtained in micro-fluidic focus area prominent
It achieves out, but realizes and can have both above-mentioned advantage simultaneously by a kind of micro-fluidic focus device there are still huge challenges: as sheath fluid presss from both sides stream skill
Art faces the introducing of high-throughput sheath liquid stream, and is applied to particle in micro-fluidic chip to focus to be in two-dimensional plane state more；It is actively poly-
Burnt technology then needs huge, expensive external equipment, and general flux is lower, cumbersome.In contrast, as a kind of typical case
Passive focusing technology, micro-fluidic (Inertial Microfluidic) the ingenious inertia effect using minute yardstick fluid of inertia
The accurate manipulation that (inertia migration and cross section Dean stream) realizes Particles Moving state and equilbrium position, has flow passage structure letter
It is single, it is to obtain extensive concern in recent years without the significant advantages such as outfield force and processing flux height without sheath fluid folder stream
A kind of micro-nano biomone control method.
However, existing inertia focusing technology is particle to be arranged in two or more equilbrium positions, and gather mostly
Burnt equilbrium position is close to runner wall surface, and tradition is unilateral or the symmetrical bilateral reducing and expansion runner of plane, helical flow path and asymmetric sine flow
The structures such as road are only capable of one group of Dean vortex of inductive formation in the transverse direction in sprue section, and causing particle to focus, there are two
Equilbrium position, and equilbrium position is also easy to produce scattering of the wall surface to detection light beam close to wall surface, limit conventional flow cell art or
The application of other optical detection means.In consideration of it, the invention patent designs a kind of three-dimensional reducing and expansion new structure, and one is proposed accordingly
Kind multidirectional induction Dean stream manipulation biomone is single-row, kernel of section position focus method, can be the essence of tumour cell in blood
Quasi- detection provides important sample prefocus unit, realizes flow cytometer detection accuracy and sensitivity with simple flow passage structure and control method
Be substantially improved.
Summary of the invention:
Patent of invention purpose: the shortcoming in view of the above technology provides one kind and overcomes existing inertia micro-fluidic device
Deficiency when manipulating particle and focusing there are multiple focusing equilbrium positions and equilbrium position close to runner wall surface, realization biological cell
In the single-row accurate focusing of cross section of fluid channel center position, the more of important sample prefocus unit are provided for high-precision flow cytometer detection
To the induction Dean three-dimensional reducing and expansion micro-fluidic device flowed and method.
Technical solution: to achieve the above object, the three-dimensional reducing and expansion micro-fluidic device of multidirectional induction Dean stream of the invention, it
Be equipped with three-dimensional reducing and expansion runner including micro-fluidic chip, in micro-fluidic chip, the head and the tail both ends of three-dimensional reducing and expansion runner be respectively equipped with
The micro-fluidic chip external world together with inlet connector and Outlet connector, inlet connector be equipped with entry conductor, outlet connection
Device is equipped with delivery channel；Wherein three-dimensional reducing and expansion runner includes the mainstream for the rectangular channel structure being arranged in micro-fluidic chip
The section in road, sprue is square or depth-to-width ratio is not 1 rectangle, entering for cylindrical space at the inlet connector of sprue
Mouthful, it is the outlet of cylindrical space at the Outlet connector of sprue, wherein the upstream between the middle part and entrance of sprue is square
Shape structure, the downstream between the middle part and outlet of sprue is equipped with polycondensation-expansion structure, between polycondensation-expansion structure and outlet
There are distances.
Polycondensation-the expansion structure includes the bulge-structure or sunk structure in the setting of sprue outside spacers.
The bulge-structure, which is included at the top of sprue, is equipped with array of protrusions, and the side of sprue is equipped with array of protrusions,
Wherein array of protrusions and array of protrusions are arranged in a one-to-one correspondence in axial coordinate；
Mirror image is equipped with array of protrusions, array of protrusions and raised battle array on the another side of the respective protrusions array on sprue
Column and array of protrusions are arranged in a one-to-one correspondence in axial coordinate.
Upper mirror image is equipped with array of protrusions, the mirror image on sprue on the another side of the respective protrusions array on sprue
It is respectively equipped with array of protrusions on another side equipped with array of protrusions and ultimately forms array of depressions, array of protrusions, array of protrusions, protrusion
Array and array of protrusions are arranged in a one-to-one correspondence in axial coordinate.
The sectional dimension of sprue is 200 × 200 μm；The array of protrusions, array of protrusions, array of protrusions and array of protrusions
For multiple spaced rectangular preiections, the size of rectangular preiection is 200 × 50 × 50 μm, between rectangular preiection between 50 μ of spacing
m。
The sunk structure is the rectangular depression being arranged at the top of sprue with unilateral side wall or two sidewalls and bottom.
A kind of three-dimensional reducing and expansion microfluidic control method of multidirectional induction Dean stream, the steps include: tumour cell utilizing fluorescence
Label, and it is mixed and made into initial mixing sample with non-fluorescent label background leucocyte, it is in random dispersion state by initial mixing sample
Sequence imports three-dimensional reducing and expansion runner by entry conductor and inlet connector, through sprue upstream end rectangle in three-dimensional reducing and expansion runner
Inertia lift acts in cross-sectional passage, drives leucocyte and tumour cell to do lateral transfer campaign, thus by leucocyte and tumour
Cell focuses to four equilbrium positions at three-dimensional four wall surface center of reducing and expansion runner, and in three-dimensional reducing and expansion runner middle and lower reaches
Place, collectively forms reducing and expansion structure by sprue and lateral projections array, top bump array, the raised battle array positioned at sprue side
It is listed in the two Dean vortex symmetrical above and below of inductive formation in the transverse direction of three-dimensional reducing and expansion cross section of fluid channel；At the top of sprue
Array of protrusions on the longitudinal direction of three-dimensional reducing and expansion cross section of fluid channel inductive formation symmetrical two Dean vortex, transverse direction side
The two Dean vortex generated to two Dean of generation vortex and longitudinal direction is mutually coupled, and forms new complicated Dean stream mould
Formula, to make leucocyte and tumour cell are mobile in such a way that the accurate inertia in single-row, kernel of section position focuses to form single-row gather
Burnt particle beam, the single-row focused particle beam that three-dimensional reducing and expansion cross section of fluid channel center is formed using external flow-through assay device
Stream is detected, and the fluorescence excitation-emission that tumour cell is issued by external flow-through assay device goes out to emit light, and by external streaming
Detection device receives identification, completes accurate counting to tumour cell, subsequent focused particle beam through outlet, Outlet connector, go out
Mouth conduit sequence exports, and is collected by waste collecting device.
The utility model has the advantages that the present invention can be cut by the way that array of protrusions is arranged simultaneously in the side of sprue and top in sprue
Inductive formation Dean is vortexed simultaneously on the transverse direction and longitudinal direction direction in face, and a kind of completely new complexity is formed after multidirectional Dean eddy
Dean vortex pattern, thus efficient manipulation biological cell, realization biological cell is single-row, kernel of section position precisely focuses；Biology
The single-row focusing of cell can ensure that each cell particle system excitation beam focal point after testing；Focal position is cut positioned at runner
It can effectively avoid the scattering that flow path wall faces detection system light beam at the center of face, so that the precision and spirit of optical detection be substantially improved
Sensitivity provides important sample prefocus unit for high-precision flow cytometer detection；Furthermore of the invention without sheath fluid folder stream or outer
The advantages of field force, micromation at low cost, easy to operate, easy of integration, can be widely used for clinical diagnosis, biological study, biochemical point
The fields such as analysis, are particularly suitable for the early detection of circulating tumor cell in blood (Circulating Tumor Cells, CTCs)
Aspect.
Detailed description of the invention:
Fig. 1 is the structural schematic diagram of the three-dimensional reducing and expansion micro-fluidic device of the multidirectional induction Dean stream of the present invention；
Fig. 2 is the three-dimensional reducing and expansion flow passage structure signal of the three-dimensional reducing and expansion micro-fluidic device of the multidirectional induction Dean stream of the present invention
Figure；
Fig. 3 is that the three-dimensional reducing and expansion cross section of fluid channel of the three-dimensional reducing and expansion micro-fluidic device of the multidirectional induction Dean stream of the present invention is multidirectional
Dean stream generates and coupling schematic diagram；
Fig. 4 is the inertia focusing principle schematic diagram of the three-dimensional reducing and expansion micro-fluidic device of the multidirectional induction Dean stream of the present invention；
Fig. 5 is the three-dimensional reducing and expansion micro-fluidic device structural schematic diagram of the multidirectional induction Dean stream of the present invention；
Fig. 6 is the three-dimensional reducing and expansion micro-fluidic device structural schematic diagram of the multidirectional induction Dean stream of the present invention.
Specific embodiment:
It elaborates with reference to the accompanying drawing to a specific embodiment of the invention.
As depicted in figs. 1 and 2, the three-dimensional reducing and expansion micro-fluidic device 1 of multidirectional induction Dean of the invention stream includes micro-fluidic
Chip 2, is equipped with three-dimensional reducing and expansion runner 5 in micro-fluidic chip 2, the head and the tail both ends of three-dimensional reducing and expansion runner 5 be respectively equipped with it is micro-fluidic
Chip 2 it is extraneous together with inlet connector 4 and Outlet connector 6, inlet connector 4 is equipped with entry conductor 3, Outlet connector
6 are equipped with delivery channel 7；Wherein three-dimensional reducing and expansion runner 5 includes the mainstream for the rectangular channel structure being arranged in micro-fluidic chip 2
The section in road 52, sprue 52 is square or depth-to-width ratio is not 1 rectangle, is cylinder at the inlet connector 4 of sprue 52
The entrance 51 in space is the outlet 54 of cylindrical space at the Outlet connector 6 of sprue 52, wherein the middle part of sprue 52 with enter
Upstream between mouth 51 is rectangular configuration, and the downstream between the middle part and outlet 54 of sprue 52 is equipped with polycondensation-expansion structure,
There are distances between polycondensation-expansion structure and outlet 54.
As shown in figure 5, mirror image is equipped with array of protrusions on the another side of the respective protrusions array 531 on sprue 52
533, array of protrusions 533 is arranged in a one-to-one correspondence in axial coordinate with array of protrusions 531 and array of protrusions 532.
As shown in fig. 6, upper mirror image is equipped with array of protrusions on the another side of the respective protrusions array 531 on sprue 52
533, it is equipped with mirror image on the another side of array of protrusions 532 on sprue 52 and is equipped with array of protrusions 534, array of protrusions 531, protrusion
Array 532, array of protrusions 533 and array of protrusions 534 are arranged in a one-to-one correspondence in axial coordinate.
The sectional dimension of sprue 52 is 200 × 200 μm；The array of protrusions 531, array of protrusions 532, array of protrusions
533 and array of protrusions 534 be multiple spaced rectangular preiections, the size of rectangular preiection is 200 × 50 × 50 μm, and rectangle is convex
50 μm of spacing between rising,
A kind of three-dimensional reducing and expansion microfluidic control method of multidirectional induction Dean stream, the steps include: tumour cell 9 utilizing fluorescence
Label, and it is mixed and made into initial mixing sample with non-fluorescent label background leucocyte 8, it is in random dispersion state by initial mixing sample
Sequence imports three-dimensional reducing and expansion runner 5 by entry conductor 3 and inlet connector 4, as shown in figure 4, through in three-dimensional reducing and expansion runner (5)
Inertia lift acts in sprue (52) upstream end rectangular section channel, drives leucocyte (8) to do with tumour cell (9) and laterally moves
Leucocyte (8) and tumour cell (9) are thus focused to four at three-dimensional (5) four wall surface center of reducing and expansion runner by shifting movement
A equilbrium position, and at three-dimensional 5 middle and lower reaches of reducing and expansion runner, reducing and expansion are collectively formed by sprue and side, top bump array
Structure, positioned at sprue side array of protrusions in the transverse direction in three-dimensional 5 section of reducing and expansion runner inductive formation it is symmetrical above and below
Two Dean vortex；Array of protrusions at the top of sprue induces life on the longitudinal direction in three-dimensional 5 section of reducing and expansion runner
It is vortexed at symmetrical two Dean；As shown in figure 4, what two Dean vortex and longitudinal direction that transverse direction generates generated
Two Dean vortex are mutually coupled, and form new complicated Dean stream mode, so that leucocyte 8 and 9 inertia of tumour cell be made to focus
Movement forms single-row focused particle line in such a way that single-row, kernel of section position precisely focuses, and is filled using external flow cytometer detection
It sets the single-row focused particle beam stream for forming three-dimensional 5 kernel of section position of reducing and expansion runner to detect, tumour cell 9 is flowed by outside
The fluorescence excitation-emission that formula detection device issues, which goes out, emits light, and is received and identify by external flow-through assay device, completes to tumour
The accurate counting of cell 9, subsequent focused particle beam are sequentially exported through outlet 54, Outlet connector 6, delivery channel 7, and by waste liquid
Collection device is collected.
Embodiment 1:
In the present embodiment it is multidirectional induction Dean stream three-dimensional reducing and expansion micro-fluidic device 1 using polydimethylsiloxane,
The materials such as polymetylmethacrylate, polycarbonate are prepared by soft lithographic processing technology, which specifically includes light
Carve SU-8 formpiston, PDMS casting and PDMS- glass bonding and etc., have many advantages, such as that machining accuracy is high；Also silica gel can be used
The materials such as film, poly terephthalic acid class plastics PET film, polyvinylchloride film are prepared by laser micro process, should
Technique specifically include laser cutting remove molding, plasma surface treatment, bonding and fixture encapsulation and etc., have production
At low cost, the advantages that process-cycle is short.In addition, other materials such as glass, silicon, metal also can be used in the flow passage structure in the present embodiment
Matter is realized by micro-processing technologies such as wet process/deep reaction ion etching, ultraprecise machining, photosensitive circuit plate etchings.
Device described in the present embodiment is mainly used for the accurate focusing and streaming inspection of haemocyte and circulating tumor cell in blood
Survey, can also be applied to other body fluid such as urine, saliva, hydrothorax, in ascites biological cell focus detection, can also expand application
The efficient inertia manipulation of micro-and nano-particles under other environment.
It is illustrated in figure 3 the schematic illustration of the multidirectional induction Dean stream of three-dimensional reducing and expansion runner.In three-dimensional reducing and expansion runner 5
Downstream area, by sprue 52, the array of protrusions 531 positioned at 52 side of sprue, the array of protrusions positioned at 52 top of sprue
532 collectively form three-dimensional reducing and expansion structure.Under this structure, when fluid flows through, the array of protrusions 531 positioned at side can be in sprue
The Dean vortex that one group of inductive formation symmetrical above and below in the transverse direction of 52 cross sections；Array of protrusions 532 positioned at top can be
One group of symmetrical Dean vortex is generated on the longitudinal direction of 52 cross section of sprue.Pass through the raised battle array of regulation sprue 52/
The parameters such as the structure size of 531/ array of protrusions 532 of column and sample flow rate can adjust the intensity and pattern of two groups of Dean vortex.
Two groups of Dean vortex is overlapped mutually coupling, and the Dean for generating a kind of complexity is vortexed new model (such as Fig. 3 right figure show pinching section section
Face flow field simulation), so as to provide a kind of completely new means for micro-and nano-particles efficient manipulation, cut biological cell in sprue 52
The single-row accurate focusing of face center is possibly realized.
It is illustrated in figure 4 cracking blood middle leukocytes 8 and tumour cell 9 precisely focusing in three-dimensional reducing and expansion runner 5
Journey.Unstressed configuration stain leukocytes 8 mix sample with fluorescent staining tumour cell 9 and inject from entry conductor 3 and inlet connector 4
It afterwards, is in random dispersion state at entrance 51.Then in the upstream region of sprue 52, classical theory is manipulated according to inertia, by used
Property lift FLInertia lift F is induced containing the wall surface for being directed toward runner centerLWWith the shear-induced inertia lift F for being directed toward runner wall surfaceLS
Lateral transfer occurs for effect, and gradually focuses to close to the equilbrium position everywhere at four wall surface centers.Then in sprue 52 under
Trip part collectively constitutes the reducing and expansion structural region with three-dimensional polycondensation-extension feature with array of protrusions 531, array of protrusions 532, with
It is multidirectional coupling complexity Dean vortex introducing, cell particle except receive inertia lift act in addition to, will also be by additional Dean
Drag FDEffect.By adjusting flow passage structure size and sample flow rate, leucocyte 8 and tumour cell 9 can be driven gradually to mainstream
It is migrated at the kernel of section in road 52, the final single-row accurate focusing for realizing runner center.In the raised battle array of array of protrusions 531/
Detection zone between column 532 and outlet 54, the excitation beam vertical irradiation of external optical detection system in focused particle beam, this
When fluorescent staining tumour cell 9 be stimulated and launch transmitting light, be detected examining system and receive identification；And unstressed configuration dyeing is white thin
Born of the same parents 8 do not inspire fluorescence, to realize that the detection to tumour cell 9 counts.Since the three-dimensional reducing and expansion runner that the present invention designs can
Single-row, kernel of section position accurate focusing is realized, wherein single-row focusing can ensure that each cell particle passes through detection system
The focus of excitation beam, and focal position is in cross section of fluid channel center can effectively avoid flow path wall in face of detection system excitation beam
Scattering, therefore can largely promote the precision and sensitivity of flow cytometer detection on the whole.
Itd is proposed in the present embodiment can multidirectional induction Dean flow three-dimensional reducing and expansion micro-fluidic device and can break through conventional inertia miniflow
Control device is only capable of the inductive formation Dean in the transverse direction of section and flows, and causing particle to focus, there are two or more balance positions
It sets, and equilbrium position realizes that single beam of the biological cell in cross section of fluid channel center precisely focuses close to the limitation of runner wall surface,
Important sample prefocus unit is provided for high-precision flow cytometer detection.Meanwhile the three-dimensional reducing and expansion micro-fluidic device that the present embodiment proposes
Also have that structure is simple, processing cost is low, easy to operate, the detection advantages such as flux height, also can widely develop examined applied to clinic
The fields such as disconnected, biological analysis, biochemical analysis, are particularly suitable for the early detection of circulating tumor cell in blood, cytology water
Flat chemotherapy drug susceptibility test etc..
Embodiment 2, as shown in figure 5, the present embodiment is set in 52 side of sprue, the other side opposite with array of protrusions 531
Array of protrusions 533 is set, and the array of protrusions 533 and array of protrusions 531 are in mirror, to induce Dean in three directions
It is vortexed and couples, efficient manipulation biological cell realizes the single-row accurate focusing in kernel of section position.
Embodiment 3, as shown in fig. 6, array of protrusions 534, and the protrusion is arranged in the bottom of sprue 52 in the present embodiment
Array 534 and array of protrusions 532 are in mirror, to induce Dean to be vortexed on four direction and couple, efficient manipulation biology
Cell realizes the single-row accurate focusing in kernel of section position.
In some other embodiment, 531/ array of protrusions of array of protrusions, 532/ array of protrusions, 533/ array of protrusions
544 structures are that the rectangular depression structure that recess is arranged in sprue 52 is constituted, and three-dimensional polycondensation-expansion is formed in main flow direction
Feature is opened up, with multidirectional induction Dean stream and efficient manipulation micro-and nano-particles.
Claims (8)
1. a kind of three-dimensional reducing and expansion micro-fluidic device of multidirectional induction Dean stream, it is characterised in that: it includes micro-fluidic chip (2),
Be equipped with three-dimensional reducing and expansion runner (5) in micro-fluidic chip (2), the head and the tail both ends of three-dimensional reducing and expansion runner (5) be respectively equipped with it is micro-fluidic
Chip (2) it is extraneous together with inlet connector (4) and Outlet connector (6), inlet connector (4) equipped with entry conductor (3),
Outlet connector (6) is equipped with delivery channel (7)；Wherein three-dimensional reducing and expansion runner (5) includes being arranged in micro-fluidic chip (2)
The sprue (52) of rectangular channel structure, the section of sprue (52) is square or depth-to-width ratio is not 1 rectangle, sprue
(52) it is the entrance (51) of cylindrical space at inlet connector (4), is that cylinder is empty at the Outlet connector (6) of sprue (52)
Between outlet (54), wherein the upstream between the middle part of sprue (52) and entrance (51) be rectangular configuration, in sprue (52)
Middle part and outlet (54) between downstream be equipped with polycondensation-expansion structure, polycondensation-expansion structure with export (54) between there are away from
From.
2. the three-dimensional reducing and expansion micro-fluidic device of multidirectional induction Dean stream according to claim 1, it is characterised in that: described
Polycondensation-expansion structure is included in the bulge-structure or sunk structure of sprue (52) outside spacers setting.
3. the three-dimensional reducing and expansion micro-fluidic device of multidirectional induction Dean stream according to claim 1, it is characterised in that: described
Bulge-structure, which is included at the top of sprue (52), is equipped with array of protrusions (532), and the side of sprue (52) is equipped with array of protrusions
(531), wherein array of protrusions (531) is arranged in a one-to-one correspondence in axial coordinate with array of protrusions (532).
4. it is according to claim 2 it is multidirectional induction Dean stream three-dimensional reducing and expansion micro-fluidic device, it is characterised in that: it is described
On sprue (52) on the another side of respective protrusions array (531) mirror image be equipped with array of protrusions (533), array of protrusions (533) with
Array of protrusions (531) is arranged in a one-to-one correspondence in axial coordinate with array of protrusions (532).
5. it is according to claim 2 it is multidirectional induction Dean stream three-dimensional reducing and expansion micro-fluidic device, it is characterised in that: it is described
Upper mirror image is equipped with array of protrusions (533) on the another side of respective protrusions array (531) on sprue (52), on sprue (52)
Mirror image is equipped on the another side of array of protrusions (532) and is respectively equipped with array of protrusions (534) and ultimately forms array of depressions, array of protrusions
(531), array of protrusions (532), array of protrusions (533) and array of protrusions (534) are arranged in a one-to-one correspondence in axial coordinate.
6. the three-dimensional reducing and expansion micro-fluidic device of multidirectional induction Dean stream, feature according to any of the above-described claim exist
In: the sectional dimension of sprue (52) is 200 × 200 μm；The array of protrusions (531), array of protrusions (532), array of protrusions
(533) and array of protrusions (534) is multiple spaced rectangular preiections, and the size of rectangular preiection is 200 × 50 × 50 μm, square
50 μm of spacing between shape protrusion.
7. the three-dimensional reducing and expansion micro-fluidic device of multidirectional induction Dean stream, feature according to any of the above-described claim exist
In: the sunk structure is rectangular depression of the setting at the top of sprue (52) with unilateral side wall or two sidewalls and bottom.
8. a kind of control method using the three-dimensional reducing and expansion micro-fluidic device of multidirectional induction Dean stream described in claim 1, special
Sign is step are as follows: tumour cell (9) are utilized fluorescent marker, and are mixed just with non-fluorescent label background leucocyte (8)
Begin mixing sample, and initial mixing sample is imported three by entry conductor (3) and inlet connector (4) in random dispersion sequence of states
It ties up reducing and expansion runner (5), inertia lift acts in sprue (52) upstream end rectangular section channel in three-dimensional reducing and expansion runner (5),
It drives leucocyte (8) and tumour cell (9) to do lateral transfer campaign, leucocyte (8) is focused to tumour cell (9) thus and is leaned on
Four equilbrium positions at nearly (5) four wall surface center of three-dimensional reducing and expansion runner, and at three-dimensional reducing and expansion runner (5) middle and lower reaches, by leading
Runner (52) and lateral projections array (531), top bump array (532) collectively form reducing and expansion structure, are located at sprue side
Array of protrusions (531) in the transverse direction in three-dimensional reducing and expansion runner (5) section inductive formation two whirlpools Dean symmetrical above and below
Stream；Array of protrusions (532) at the top of sprue inductive formation or so on the longitudinal direction in three-dimensional reducing and expansion runner (5) section
Symmetrical two Dean vortex, two Dean vortex that transverse direction generates and two Dean vortex that longitudinal direction generates are mutual
Coupling, forms new complicated Dean stream mode, to make leucocyte (8) and tumour cell (9) in single-row, kernel of section position essence
The mode movement that quasi- inertia focuses forms single-row focused particle line, using external flow-through assay device to three-dimensional reducing and expansion runner
(5) the single-row focused particle beam stream that kernel of section position is formed is detected, and tumour cell (9) is sent out by external flow-through assay device
Fluorescence excitation-emission out, which goes out, emits light, and is received and identify by external flow-through assay device, completes to the accurate of tumour cell (9)
It counts, subsequent focused particle beam is exported (54), Outlet connector (6), delivery channel (7) sequence export, and by waste collection
Device is collected.
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Cited By (7)
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